+    *•'% 

I     * 


I 


THE 

COMMON  BACTERIAL  INFECTIONS 
OF  THE  DIGESTIVE  TEACT  • 

AND    THE    INTOXICATIONS 
ARISING  FROM  THEM 


BY 


C.   A.    HERTER,  M.D. 

PROFESSOR    OF   PHARMACOLOGY   AND    THERAPEUTICS    IN 

COLUMBIA    UNIVERSITY,    CONSULTING   PHYSICIAN 

TO   THE    CITY   HOSPITAL,    NEW   YORK 


gorfe 
THE   MACMILLAN   COMPANY 

LONDON:  MACMILLAN  &  CO.,  LTD. 
1907 

All  rights  reserved 


COPYRIGHT,  190T, 
BT  THE  MACMILLAN  COMPANY. 


Set  up  and  electrotyped.    Published  April,  1907. 


J.  S.  Cashing  &  Co.  —  Berwick  &  Smith  Co. 
Norwood,  Mass.,  U.S.A. 


PREFACE 

THIS  little  volume  embodies  views  recently  presented 
at  the  New  York  Academy  of  Medicine,  in  a  lecture 
before  the  Harvey  Society  for  the  Diffusion  of  Medical 
Knowledge.  Although  the  data  on  which  this  lecture 
was  based  have  been  summarized  in  another  publication, 
I  wish  to  present  them  more  fully  in  the  present  volume 
in  order  that  some  important  details,  not  suited  for  pub- 
lication in  a  medical  journal,  may  be  brought  to  the 
notice  of  practitioners  and  investigators.  The  book 
does  not  aim  at  a  systematic  discussion  of  the  extended 
and  somewhat  confused  field  of  gastro-enteric  infection, 
either  from  a  clinical  or  a  bacteriological  standpoint. 
Neither  does  it  make  any  claim  to  present  fully  the  lit- 
erature of  this  subject. 

I  have  laid  considerable  stress  on  methods  developed 
in  my  laboratory  with  a  view  to  obtaining  a  better  insight 
into  the  bacterial  conditions  of  the  digestive  tract  than 
has  been  hitherto  possible.  This  I  have  done  in  the  belief 
that  when  these  methods  are  utilized  in  practice  they  will 
prove  of  real  service  in  gaining  a  truer  conception  of  the 
nature  of  the  bacterial  processes  that  are  operative  in 
disease.  I  am  confident  that  the  painstaking  application 
of  these  methods  will  furnish  practitioners  with  new  and 

535528 


vi  PREFACE 

reliable  indications  as  to  the  progress  of  many  cases  of 
infection  of  the  digestive  tract. 

Without  the  cooperation  of  my  associates  I  could  not 
have  obtained  the  data  given  in  this  volume.  I  am  under 
especial  obligations  to  Dr.  Helen  Baldwin,  Miss  M.  L. 
Foster,  Dr.  A.  J.  Wakeman,  Mr.  H.  C.  Ward,  and  Dr. 
William  R.  Williams  for  the  efficient  help  which  they 
have  in  various  directions  given  me. 

DECEMBER  1,  1906. 


CONTENTS 

PAGE 

GENERAL  CONSIDERATIONS  RELATIVE  TO  THE  BACTERIAL 
FLORA   OF    THE  HUMAN    DIGESTIVE   TRACT   IN 

HEALTH 1 

Defensive  Action  of  the  Digestive  Juices     ...        6 
On  the  Antagonism  between  B.  coli  communis  and  Other 

Microorganisms 7 

Criticism  of  Experiments  of  Conradi  and  Kurpjuweit        17 
Influence  of  Reaction  on  the  Growth  and  Products  of 

Intestinal  Anaerobes         ......      21 

Aerobic  and  Anaerobic  Conditions  in  the  Digestive  Tract      23 
The  Bacteria  of  the  Human  Digestive  Tract  at  Different 

Ages  in  Apparently  Healthy  Individuals         .     •  .      35 

THE  BACTERIAL  PROCESSES  IN  THE  DIGESTIVE  TRACT  OF 

NORMAL  NURSLINGS  AND  BOTTLE-FED  INFANTS        37 
Nursling  Infants    ........      37 

Distribution  of  the  Bacterial  Flora  in  the  Digestive 

Tract  of  the  Nursling 48 

The  Infection  of  the  Nursling's  Digestive  Tract  and 
the  Relation  of  the  Microorganisms  to  the  Perma- 
nent Bacterial  Flora 53 

Bacterial  Flora  of  Bottle-fed  Children  .        .        .        .59 
Products  of  Decomposition  in  the  Intestinal  Tract  of 

Bottle-fed  Children 64 

Action  of  the  Mixed  Faecal  Flora  upon  Various  Media      66 

THE   BACTERIAL  CONDITIONS  IN  THE  DIGESTIVE   TRACT 
DURING  CHILDHOOD,  ADOLESCENCE,  ADULT  LIFE, 

AND  SENESCENCE 69 

Period  of  Childhood  and  Adolescence  .        .        .         .69 

Period  of  Adult  Life 72 

Period  of  Senescence  .        .75 


viii  CONTENTS 

PAGB 

CHARACTERS  OF  THE  BACTERIAL  FLORA  OF  CARNIVOROUS 

AND  OF  HERBIVOROUS  ANIMALS    ....  80 

Influence  of  Food  on  Human  Bacterial  Flora  of  the  Digest- 
ive Tract 86 

The  Reducing  Action  of  Meat 89 

The  Influence  of  the  Epithelial  Cells  Lining  the  Digestive 

Tract 91 

The  Permeability  of  the  Mucous  Membrane  of  the  Intes- 
tinal Tract  for  Bacteria 93 

Phylogenetic  Significance  of  the  Large  Intestine       .        .  97 
The  Importance  of  Prompt  Resorption  from  the  Small 

Intestine 99 

The  Phenomenon  of  Substitution 100 

The  Presence  of  Pathogenic  Bacteria  in  the  Digestive 

Tract  in  Health 102 

CRITERIA   EMPLOYED    IN   THE   CLASSIFICATION   OF   BAC- 
TERIA OF  THE  GASTRO-ENTERIC  TRACT        .        .  105 

Methods  of  Investigation Ill 

Character  of  the  Microscopical  Fields  ....  Ill 
The  Dimethylamidobenzaldehyde  Reaction  of  the 

Faeces 145 

The  Dimethylamidobenzaldehyde  Reaction  of  the 

Urine 147 

COMMON  BACTERIAL  INFECTIONS  OF  THE  DIGESTIVE  TRACT, 
CONSIDERED    FROM    THE    STANDPOINT    OF    THE 

MICROORGANISMS 150 

The  Colon-typhoid-dysentery  Group 150 

Colon  Bacilli 150 

Typhoid  Bacilli 157 

Paratyphoid  and  Allied  Infections        ....  167 

Dysentery  Bacilli  . 172 

Liquefying  Bacteria 181 

Streptococcal  and  Staphylococcal  Infections      .        .        .  185 

Bacillus  Bifidus 190 

Infections  through  Anaerobic  Bacteria      .        .        .        .191 
Bacillus  Putrificus          .        .        .        .        .        .        .192 


CONTENTS  ix 

PAGE 

Bacillus  A  erogenes  Capsulatus 196 

Bacillus  Botulinus 210 

THE  FERMENTATIVE  AND  PUTREFACTIVE  PROCESSES  PROM 

THE  STANDPOINT  OF  THEIR  PRODUCTS          .        .  214 

Oxalic  Acid  and  Oxaluria 216 

Acetone           . 218 

Basic  Substances 221 

Putrescin  and  Cadaverin 224 

Sulphur  Compounds 226 

Mercaptan 226 

Hydrogen  Sulphide 227 

Hydrogen  Sulphide  and  its  Relation  to  Enterogenic 

Cyanosis 234 

Aromatic  Products  of  Putrefactive  Decomposition    .        .  237 

Phenol  and  Cresol 237 

Skatol 239 

Indol 241 

Indicanuria          .........  257 

The  Possibility  of  the  Occurrence  of    Indolsemia  and 

Indoluria 269 

Indigouria 272 

Individual  Susceptibilities  to  Different  Enterogenous 
Poisons  as  Possible  Factors  in  Determining  Clini- 
cal Types 274 

TYPES  OF  CHRONIC  EXCESSIVE  INTESTINAL  PUTREFACTION  278 

I.     The  Indolic  Type  of  Chronic  Excessive  Intestinal 

Putrefaction 280 

II.     The  Saccharo-butyric  Type  of  Chronic  Excessive 

Intestinal  Putrefaction 291 

III.    The  Combined  Indolic  and  Saccharo-butyric  Type 

of  Chronic  Excessive  Intestinal  Putrefaction           .  306 

METHODS  RELATING  TO  THE  MODIFICATION  AND  CONTROL 
OF  BACTERIAL  PROCESSES  CONCERNED  IN  CHRONIC 

EXCESSIVE  INTESTINAL  PUTREFACTION        .        .  314 
The  Avoidance  of  Putrefactive  Contamination  of  the 

Food  .        .        .317 


x  CONTENTS 

PAGE 

The  Promotion  of  Prompt  Digestion  and  Absorption 

in  the  Small  Intestine 322 

Methods  designed  to  reduce  the  Numbers  of  Putre- 
factive Anaerobes 329 

SOCIOLOGICAL  CONSIDERATIONS 347 

INDEX ,353 


THE   COMMON   BACTERIAL  INFECTIONS 
OF  THE  DIGESTIVE   TRACT 


THE  COMMON  BACTEEIAL  INFECTIONS 
OF  THE  DIGESTIVE  TEACT 

GENERAL  CONSIDERATIONS  RELATIVE  TO  THE 
BACTERIAL  FLORA  OF  THE  HUMAN  DIGEST- 
IVE TRACT  IN  HEALTH 

IF  one  examines  with  the  microscope  the  contents  of 
any  portion  of  the  large  intestine  of  a  human  being  or 
of  any  mammal,  the  richness  of  the  material  in  micro- 
organisms is  strikingly  apparent,  especially  in  stained 
preparations.  Their  number  has  been  estimated  at 
one  hundred  and  twenty-six  billions  for  the  daily  human 
excreta.  It  is  true  that  if  the  material  is  selected  from 
the  lowest  portion  of  the  gut,  many  of  the  microorgan- 
isms of  a  cultivable  nature  can  be  shown  by  suitable 
cultural  methods  to  be  no  longer  living,  but  rather  to 
be  undergoing  a  process  of  disintegration,  partly  owing 
to  a  solution  in  their  own  juices  —  a  process  of  autoly- 
sis.  But  even  the  dead  and  dying  bacterial  inhabitants 
of  the  lower  intestinal  tract  point  to  the  multiplicity 
of  bacterial  life  at  higher  levels.1  And  not  only  are  these 

1  Strasburger,  J.,  "  Untersuchungen  tiber  die  Bakterienmenge 
in  menschlichen  Faces/'  Zeitschr.  f.  klin.  Med.,  xlvi,  p.  413,  1902. 

It  has  been  estimated  that  the  proportion  of  dead  bacteria  in 
normal  human  fseces  is  often  as  high  as  ninety-nine  per  cent.  It 

B  1 


£"        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

bacterial    inhabitants    numerous    but    they    represent 
many  species  and  varieties. 

The  knowledge  that  the  digestive  tract  is  so  rich  in 
bacterial  forms  of  life  has  led  many  physiologists  to 
inquire  into  the  biological  meaning  of  this  remarkable 
fact.  Pasteur  expressed  a  belief  that  these  bacterial 
inhabitants  are  essential  in  some  way  to  the  life  of  the 
individual  which  harbors  them.  Nut  tall  and  Thier- 
f elder,1  in  their  well-known  experiments,  attempted  to 
rear  guinea-pigs  delivered  by  Csesarian  section  and  fed 
on  quite  sterile  food.  As  the  animals  lived  and  increased 
in  weight,  the  experimenters  concluded  that  the  intestinal 
bacteria  are  not  essential  to  normal  nutrition.  This 
view,  as  will  be  presently  seen,  gets  support  from  the 
observations  of  Levin2, that  some  animals  of  the  Arctic 
region,  as  polar  bears,  have  no  bacteria  in  the  digestive 

appears,  however,  that  this  is  an  under-estimate  of  the  living  bac- 
teria. It  may  possibly  hold  true  of  the  aerobic  bacteria  which 
will  grow  on  ordinary  media.  But  we  know  that  there  are  often 
many  aerobes  and  anaerobes  in  the  intestine  which  do  not  grow  on 
ordinary  media.  In  some  instances  there  are  very  many  strict 
anaerobes  (e.g.  B.  aerogenes  capsulatus)  which  appear  only  on 
specially  prepared  media  on  anaerobic  plates.  These,  of  course, 
do  not  come  into  any  count  made  in  ordinary  ways.  Even  the 
numbers  of  living  colon  bacilli  are  subject  to  great  variations.  In 
the  same  individual  there  may  be  at  one  tune  a  considerable  pro- 
portion of  cultivable  (living)  bacilli.  In  a  state  of  constipation  the 
number  of  cultivable  colon  bacilli  may  become  very  small.  This 
death  of  bacteria  in  the  lower  bowel  during  constipation  doubtless 
depends  mainly  on  a  failure  of  food  supply  and  absence  of  moisture. 

1  "  Thierisches  Leben  ohne  Bakterien  im  Verdauungskanal," 
Zeitschr.  f.  physiol  Chem.,  xxi,  p.  109,  1895;  xxii,  p.  62,  1896; 
xxiii,  p.  231,  1897. 

2 "  Bakteriologische  Darmuntersuchungen,"  Skandinavisches 
Archiv  /.  Physiol.,  xvi,  p.  249,  1904. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT  3 

tract.  Even  in  temperate  regions  there  are  animals 
whose  alimentary  tracts  are  comparatively  free  from 
bacterial  life.  This  is  said  to  be  the  case  with  the  parrot. 
Other  observers  have,  however,  reached  a  different  con- 
clusion from  that  of  Nuttall  and  Thierfelder.  Schot- 
telius  *  found  that  chickens  fed  on  sterile  food  were  re- 
tarded in  development  and  showed  normal  growth  only 
when  given  food  containing  bacteria.  Similar  results 
were  obtained  by  Madam  Metchnikoff 2  in  experiments 
on  tadpoles.  Very  carefully  conducted  experiments  by 
Moro 3  on  the  larvse  of  the  turtle  (Pelobates  fureus, 
Wagler)  lead  to  the  same  conclusion;  namely,  that 
intestinal  bacteria  are  necessary  to  normal  nutrition. 

It  must  be  admitted,  I  think,  that  none  of  these  ex- 
perimental studies  are  really  conclusive  as  to  the  neces- 
sity of  bacterial  action  in  the  digestive  tract  for  the 
maintenance  of  health  in  adult  mammals  of  the  highest 
type  —  man  and  various  domestic  animals.  Experi- 
ments on  tadpoles  and  chickens  cannot  with  confidence 
be  applied  to  the  case  of  man.  The  experiments  on 
guinea-pigs  can  more  justly  perhaps  be  taken  as  typical 
for  mammals,  but  as  the  experiments  of  Nuttall  and 
Thierfelder  were  extended  over  only  a  short  period  of 
time,  they  can  hardly  be  held  to  prove  that  bacteria  are 

1  "Bedeutung  der  Darmbakterien  fur  die  Ernahrung,"  Archiv 
/.  Hyg.,  xlii,  p.  48,  1902. 

2  "Note  sur  I'influence  des  microbes  dans  le  development  des 
tetards,"  Ann.  de  I'Inst.  Past.,  xv,  p.  631,  1901. 

3  "  Morphologische  und  biologische  Untersuchungen  iiber  die 
Darmbakterien    des    Sauglings,"  IV.   "Der  Schottelius  Versuch 
am  Kaltbltiter,"  Jahrb.  /.  Kinderheilk.,  xii,  p.  467,  1905. 


4          INFECTIONS  OF  THE  DIGESTIVE  TRACT 

either  essential  or  non-essential  to  the  maintenance  of 
prolonged  health  during  the  period  of  adult  existence. 
The  evidence  given  by  the  sterile  intestinal  contents 
of  certain  Arctic  animals  is  apparently  conclusive  for 
the  conditions  in  which  this  experiment  of  nature  has 
been  carried  out.  Here  we  have  animals  born  and  living 
in  surroundings  where  bacteria  are  very  few  in  number, 
and  it  is  probably  on  account  of  the  great  rarity  of  micro- 
organisms in  the  air  and  the  small  number  in  the  water l 
that  the  intestinal  contents  contain  so  few  bacteria. 
These  animals  are  able  to  live  indefinitely  in  a  state  of 
robust  health.  Levin  examined  the  intestinal  contents 
of  Arctic  animals  in  Spitzenberg.  The  digestive  tract 
was  found  to  be  in  most  instances  entirely  sterile  in 
white  bears,  seals,  reindeer,  eider  ducks,  penguins,  etc., 
although  very  small  numbers  of  organisms  resembling 
the  colon  bacillus  were  found  in  one  white  bear  and  in 
two  seals  which  were  examined. 

Clearly  then,  in  this  case,  the  intestinal  bacteria  are 
not  required  to  carry  on  the  ordinary  digestive  processes 
and  normal  nutrition.  It  has  been  supposed  that  the 
intestinal  bacteria  aid  in  the  digestion  of  cellulose,  which 
they  are  undoubtedly  able  to  decompose  fermentatively. 
The  argument  in  favor  of  the  importance  of  this  function 
of  the  intestinal  bacteria  loses  much  of  its  force  if  it  be 
true,  as  lately  maintained  by  Bergman,2  that  most  of  the 

1  It  was  estimated  that  there  was  one  organism  in  11  c.c.  of 
water,  whereas  in  the  river  Seine  it  was  estimated  that  there  are 
about  2,000,000  in  the  same  volume  of  water. 

2"Studien  tiber  die  Digestion  der  Pflanzenfresser,"  Skandir 
navisches  Archiv  /.  Physiol.,  xviii,  p.  119,  1906. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT          5 

cellulose  eaten  by  herbivora  (in  which  the  digestive 
function  of  the  bacteria  chiefly  comes  into  question)  is 
provided  with  intracellular  enzymes  capable  of  decom- 
posing cellulose. 

The  real  significance  of  the  normal  intestinal  flora 
probably  lies  not  in  any  immediate  relation  to  processes 
of  digestion,  but  in  a  wholly  different  direction. 

It  is  impossible  to  avoid  the  entrance  of  bacteria  into 
the  digestive  tract.  As  will  be  seen  when  we  come  to 
consider  the  normal  flora  of  the  alimentary  tract,  the 
obligate  bacteria  (e.g.  B.  lactis  aerogenes,  B.  coli,  B. 
bifidus)  have  adapted  themselves  to  the  secretions  of 
this  part  of  the  body  and  ordinarily  hold  their  own 
against  new-comers.  By  virtue  of  their  adaptation 
they  are  not  ordinarily  harmful  to  their  host,  but  on 
the  contrary,  they  are  under  some  circumstances  cap- 
able of  doing  a  service  by  giving  rise  to  conditions  that 
discourage  the  growth  of  many  harmless  and  harmful 
species  which  the  human  animal  cannot  readily  exclude 
from  his  digestive  tract.  I  believe  the  chief  significance 
of  the  obligate  intestinal  bacteria  lies  in  their  potential 
capacity  for  thus  checking  the  development  of  other 
types  of  organisms  capable  of  doing  injury. 

Under  ordinary  conditions  of  life,  in  temperate  cli- 
mates, and  still  more  so  in  hot  ones,  a  human  being  is 
liable  to  take  into  the  alimentary  tract,  with  food  and 
drink,  microorganisms  which  are  capable  of  doing  injury 
if  they  find  opportunity  to  multiply  in  the  digestive 
tract.  Water,  milk,  cheese,  oysters,  game,  preserved 
and  fresh  meats,  etc.,  are  liable  to  contain  injurious 


6          INFECTIONS  OF  THE  DIGESTIVE  TRACT 

bacteria.  Among  such  bacteria  are  pyogenic  strepto- 
cocci and  staphylococci,  the  paratyphoid  bacilli,  typhoid 
bacilli,  the  dysentery  bacilli,  proteus  vulgaris,  and  the 
spore-bearing  anaerobes  —  B.  putrificus  (Bienstock), 
B.  aerogenes  capsulatus,  B.  botulinus,  etc. 

Defensive  Action  of  the  Digestive  Juices.  —  The  normal 
human  organism  is  provided  with  more  or  less  efficient 
(though  by  no  means  fully  understood)  methods  of  de- 
fense against  these  bacterial  invaders.  The  secretion 
of  the  gastric  juice  in  normal  abundance,  after  a  meal, 
provides  a  degree  of  acidity  which  acts  as  an  effective 
check  upon  the  growth'of  many  non-sporula ting  bacteria, 
and  is  actually  destructive  to  most  varieties  at  least  in 
a  measure.  Probably  the  proteolytic  action  of  the  pep- 
tic ferment  and  the  tryptic  enzymes  leads  to  a  very 
quick  destruction  of  any  bacteria  whose  vitality  has 
been  lowered  by  contact  with  the  acid  of  the  gastric 
juice.  If,  however,  bacteria  are  administered  in  very 
large  numbers,  there  is  a  chance  that  a  certain  proportion 
of  them  will  run  the  gauntlet  of  these  defenses  and  find 
their  way  into  the  lower  part  of  the  small  intestine  and 
into  the  colon.  This  seems  especially  liable  to  happen 
in  those  cases  where  the  microbes  are  taken  into  the 
empty,  non-secreting  stomach,  or  into  a  stomach  with 
defective  motility  which  secretes  little  gastric  juice  with 
a  low  content  of  hydrochloric  acid  —  and  there  are  many 
such  stomachs  among  persons  over  forty  years  of  age 
and  in  fair  health.  Thus  the  bacteria  (with  any  spores 
that  may  have  developed  from  them  or  have  been  in- 
gested as  such)  find  their  way  to  the  region  of  the  colon 


INFECTIONS  OF  THE  DIGESTIVE  TRACT          7 

and  here  are  confronted  with  immense  numbers  of  the 
chief  obligate  race  of  bacteria  of  the  digestive  tract  — 
the  representatives  of  the  B.  coli  type.  Another  group 
of  obligate  organisms  closely  allied  to  B.  coli,  B.  lactis 
aerogenes,  is  present  in  the  upper  part  of  the  small 
intestine  and  becomes  gradually  less  abundant  with  its 
descent  into  the  colon  and  finally  appears  in  relatively 
small  numbers  in  the  fa3ces,  if  at  all.  As  the  bacteria 
of  the  B.lactis  aerogenes  type  grow  less  numerous,  the 
representatives  of  the  B.  coli  group  grow  more  abundant 
and  beyond  the  ileocaecal  valve  largely  dominate  the 
intestinal  flora. 

Exactly  what  happens  when  the  accidental,  sapro- 
phytic  forms  of  bacterial  life  —  the  "wild  races/'  as 
the  French  call  them  —  come  to  close  quarters  with 
the  " obligate/'  well-adapted  parasitic  forms  of  the 
intestine,  we  do  not  at  present  know.  There  are,  how- 
ever, numerous  facts  which  point  to  well-defined  bio- 
logical antagonisms  between  the  "wild"  forms  and  the 
representatives  of  the  B.  coli  group. 

ON   THE   ANTAGONISM   BETWEEN    B.    Coli  COmmunis  AND 
OTHER  MICROORGANISMS 

The  members  of  the  B.  coli  group  are  organisms  of 
varying  morphology,  characterized  by  a  certain  hardiness 
in  growth  on  ordinary  media,  by  the  free  production  of 
gas  and  acid  on  various  sugars,  by  the  coagulation  of 
milk,  and  usually  by  the  formation  of  indol,  and  by  a 
sluggish  motility  in  some  fully  grown  forms  and  active 


8          INFECTIONS  OF  THE  DIGESTIVE  TRACT 

mo  till  ty  in  members  of  young  surface  colonies.1  They 
do  not  retain  the  Gram  stain.  The  members  of  the 
B.  lactis  aerogenes  group  are  distinguished  from  those 
of  the  B.  coli  group  by  unimportant  morphological 
differences.  More  significant  differences  exist  in  respect 
to  biochemical  characters.  Among  these  differences 
are  a  somewhat  greater  ability  to  form  gas  on  sugar 
media,  a  more  rapid  coagulative  action  on  milk  (often 
with  capsule  formation),  the  ability  to  make  gas  from 
potato  starch,  the  more  frequent  failure  to  make  indol, 
and  the  greater  luxuriance  of  growth  on  gelatin.  In 
general,  then,  the  fermentative  activities  of  B.  lactis 
aerogenes  are  somewhat  greater  than  those  of  the  B. 
coli  group,  while  the  putrefactive  powers  are  distinctly 
less.  Harden 2  has  lately  shown  that  there  is  a  constant 
difference  in  the  behavior  of  B.  lactis  aerogenes  and  B. 
coli  when  grown  anaerobically  on  sugar  bouillon,  in 
regard  to  the  ratio  of  alcohol  and  acetic  acid  produced. 
This  difference  appears  to  strengthen  the  right  of  B. 
lactis  aerogenes  to  be  regarded  as  a  distinct  organism  from 
B.  colij  although  the  relationship  between  the  two  is 
close.  The  behavior  of  these  two  groups  toward  other 
organisms  is  probably  very  similar,  but  as  the  antago- 

1  For  a  detailed  discussion  of  B.  coli  communis  see  Escherich 
(Th.   Escherich   u.   M.  Pfaundler,   "Bacterium   coli   commune," 
Kolle  &  Wassermann's  "  Handbuch  der  pathogenen  Mikroorganis- 
men,"  p.  334, 1902) ;  also  Theobald  Smith  ("Note  on  Bacillus  Coli 
Communis  and  Related  Forms"),  Amer.  Journ.  of  the  Med.  Sci., 
September,  1895,  who  gives  important  data  as  to  fermentative 
characters. 

2  "The  Chemical  Action  on  Glucose  of  the  Lactose-fermenting 
Organisms  of  Faeces,"  Journ.  of  Hyg.,  v,  p.  488,  1905. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT          9 

nistic  action  of  the  B.  coli  group  has  been  more  carefully 
observed  I  shall  speak  of  this  only,  especially  as  the 
physiological  behavior  of  its  members  is  the  more  im- 
portant on  account  of  their  wider  distribution  in  the 
digestive  tract. 

The  most  far-reaching  contention  relating  to  the  defen- 
sive action  of  the  B.  coli  group  is  based  on  the  recent 
observation  of  Conradi  and  Kurpjuweit l  that  the 
members  of  this  class  make  thermostabile  and  ther- 
molabile  substances  which  have  a  powerful  antibacterial 
action,  being  still  active  hi  a  dilution  of  1  to  10,000 
parts,  and  hence  comparable  to  the  antibacterial 
action  of  carbolic  acid.  The  inhibitory  action  of  these 
substances  is  stated  to  be  not  confined  to  alien  bacteria, 
but  relates  also  to  the  B.  coli  group.  The  inhibition 
in  growth  observed  in  old  cultures  was  attributed  to  this 
substance.  Moreover,  it  was  claimed  that  it  is  owing 
to  such  bactericidal  substances  that  the  members  of  the 
B.  coli  group  tend  to  die  out  as  they  pass  toward  the 
lower  end  of  the  bowel.  It  is  easy  to  satisfy  oneself 
that  the  faeces  of  a  healthy  person  contain  more  living 
colon  bacilli  if  the  intestinal  contents  have  somewhat 
rapidly  passed  through  the  colon  than  if  the  usual  so- 
journ of  material  in  the  lower  bowel  has  occurred.  It 
is  also  noteworthy  that  relatively  few  living  representa- 
tives of  the  B.  coli  class  are  present  in  the  movements  of 
healthy  persons  with  obstinate  constipation.  The  cause 

iaUeber  die  Bedeutung  der  bakteriellen  Hemmungsstoffe  fur 
die  Physiologic  und  Pathologic  des  Darms,"  Munch,  med.  Wochen- 
schr.,  Hi,  pp.  2164,  2228,  1905. 


10        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

of  this  high  mortality  among  the  colon  bacilli  is  ascribed 
by  Conradi  and  Kurpjuweit  to  increased  opportunities 
to  make  bactericidal  substances. 

In  their  experiments  these  writers  found  that  the 
growth  of  the  typhoid  bacillus  and  of  the  paratyphoid 
bacillus  is  definitely  inhibited  by  the  activities  of  the 
colon  bacillus,  and  this  restraint  is  referred  by  them  to 
the  specific  inhibitory  products  of  the  latter  microbe. 
It  will  be  shown  in  subsequent  pages  that  the  claims  of 
Conradi  and  Kurpjuweit  have  not  been  successfully 
sustained.  The  observations  related  by  them  are  of 
great  interest,  but  the  interpretation  placed  on  them 
appears  to  be  erroneous. 

The  inhibitory  action  of  B.  coli  upon  the  putrefactive 
anaerobes  is  shared  by  a  closely  related  group  of  bacteria 
first  described  as  B.  bifidus  by  Tissier.1  This  group  of 
bacteria  was  originally  included  by  Escherich  with  the 
colon  bacilli,  but  for  reasons  which  will  be  mentioned 
later,  has  now  been  separated  from  them.  Tissier 
found  that  B.  bifidus,  under  certain  conditions,  inhibits 

1  "La  Flore  intestinale  normale  et  pathologique  du  nourrisson," 
These  de  Paris,  1900. 

There  are  certain  bacteria  that  have  the  ability  to  check  the 
growth  of  B.  coli.  Streptococci  derived  from  human  faeces  I  have 
repeatedly  observed  to  repress  the  growth  of  B.  coli  from  the  same 
individual,  in  the  anaerobic  limb  of  the  fermentation  tube.  B. 
lactis  aerogenes  may  be  repressed  in  the  same  way.  Heinemann 
("  The  Significance  of  Streptococci  in  Milk,"  Journ.  Infect.  Dis.,iii, 
p.  173,  1906)  has  found  that  streptococci  from  milk  interfere  with 
the  development  of  B.  lactis  aerogenes.  Gabricewski  and  Mal- 
jatai  ("  Ueber  die  bakterienfeindlichen  Eigenschaften  des  Cholera- 
bacillus,"  Centralbl.  f.  Bakt.,  xiii,  p.  780,  1893)  observed  that  B. 
coli  is  inhibited  by  the  growth  of  cholera  vibrios. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT        11 

the  growth  of  the  anaerobic  microbe  which  he  describes 
as  B.  perfringens  and  which  appears  to  be  no  other  than 
the  organism  known  in  the  United  States  as  B.  aerogenes 
capsulatus  (Welch)  and  in  Germany  as  the  gas-phlegmon 
bacillus  (Fraenkel). 

The  B.  bifidus  of  Tissier  is  closely  related  to  the 
organism  described  by  Moro  as  B.  acidophilus  and  shares 
with  the  latter  the  ability  to  grow  in  a  more  strongly 
acid  medium  than  can  be  withstood  by  meat  bacteria. 
Recent  studies  of  these  bacteria  by  Bjeloussow1  have 
led  him  to  identify  these  acidophile  microorganisms 
with  certain  acidophile  bacteria  studied  by  him,  and  to 
which  he,  as  well  as  Mereschkowsky,2  attaches  con- 
siderable importance  as  protective  inhabitants  of  the 
digestive  tract.  The  capacity  to  grow  in  a  medium 
containing  one-half  or  even  one  per  cent,  of  acetic  acid 
is  an  indication  that  the  acidophile  bacteria  might  as- 
sume a  dominant  position  in  the  digestive  tract  if  pro- 
vided with  suitable  food  materials  for  the  production 
of  acid.  It  is  stated  that  if  large  numbers  of  these  bac- 
teria be  administered  to  a  dog  by  mouth,  other  flora  may 
to  a  large  extent  be  temporarily  suppressed.  But  as 
in  the  case  of  feeding  other  kinds  of  microorganisms  the 
leading  part  can  only  be  maintained  by  continuously 
feeding  large  numbers  of  the  acidophiles.  Whether 

*"Zur  Biologie  und  Methodik  der  Ausscheidung  der  soge- 
nannten  acidophilen  Bakterien,"  Diss.  No.  76,  St.  Petersburg  (Rus- 
sian) . 

2"Zur  Frage  iiber  die  Rolle  der  Mikroorganismen  im  Darm- 
kanal,"  Centralbl.  /.  Bakt.  Orig.,  xxxix,  pp.  380,  581,  696,  1905, 
andxl,  p.  118,  1906. 


12        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

such  feeding  would  be  practicable  in  man  on  a  scale  suffi- 
ciently great  to  secure  definite  results  in  the  suppression 
of  harmful  types,  such  as  the  putrefactive  anaerobes, 
can  only  be  determined  by  experiment.  At  the  present 
time  it  is  known  that  the  acidophiles  are  represented  in 
all  parts  of  the  tract,  especially  in  the  large  intestine, 
but  we  cannot  yet  say  with  confidence  what  is  their 
physiological  role  or  what  would  be  their  influence  on 
the  organism  if  their  numbers  should  be  greatly  in- 
creased through  feeding. 

The  various  facts  that  have  now  been  advanced  render 
it  certain  that  microorganisms  of  the  B.  coli  type  are 
able  under  some  conditions  to  check  the  growth  of  patho- 
genic microorganisms  which  are  often  found  among  the 
intestinal  flora.  The  conditions  that  obtain  in  the  colon 
differ,  however,  with  respect  especially  to  the  nutrient 
pabulum  and  the  digestive  secretions,  from  any  attain- 
able experimental  conditions,  however  cleverly  these  may 
be  designed  to  imitate  what  occurs  in  nature.  We  have 
therefore  to  exercise  some  caution  in  transferring  these 
results,  without  due  consideration,  to  the  human  digestive 
tract.  Nevertheless  the  evidence  now  available  suggests 
that  in  health  the  colon  bacillus,  both  in  man  and  the 
higher  mammals,  exerts  an  important  function  in  com- 
bating the  development  of  the  injurious  saprophytes 
with  which  even  in  ordinary  health  the  human  intesti- 
nal tract  almost  necessarily  abounds.  A  long,  largely 
anaerobic  intestinal  tract,  permitting  gradual  resorption 
of  the  contents,  is  a  physiological  necessity  in  order  that 
a  loss  of  water  and  its  detrimental  consequences  may 


INFECTIONS  OF  THE  DIGESTIVE  TRACT        13 

be  spared  the  organism.  The  presence  in  the  colon  of 
immense  numbers  of  obligate  microorganisms  of  the 
B.  coli  type  may  be  an  important  defense  of  the  organism 
in  the  sense  that  they  hinder  the  development  of  that 
putrefactive  decomposition  which,  if  prolonged,  is  so 
injurious  to  the  organism  as  a  whole. 

We  have  in  this  adaptation  the  most  rational  explana- 
tion of  the  meaning  of  the  myriads  of  colon  bacilli  that 
inhabit  the  large  intestine.  These  bacilli  are  essential 
to  the  life  of  the  individual  mammal  as  a  defense  against 
bacterial  foes  which  it  is  impracticable  to  wholly  exclude 
from  the  digestive  tract,  and  not  as  agents  in  directly 
facilitating  the  processes  of  digestion  in  the  narrow 
sense.  This  view  is  not  inconsistent  with  the  conception 
that  under  some  conditions  the  colon  bacilli  multiply 
to  such  an  extent  as  to  prove  harmful,  through  the  part 
they  take  in  promoting  fermentation  and  putrefaction. 
It  seems  to  me  not  unlikely  that  the  reaction  of  the  fluids 
of  the  digestive  tract  may  influence  the  character  of  the 
activities  of  the  colon  bacilli,  an  alkaline  reaction  favor- 
ing their  putrefactive  functions  if  peptones  be  present. 

The  following  facts,  first  noted  by  Moro  and  Murath, 
point  to  the  existence  of  bacterial  inhibitory  powers 
on  the  part  of  the  fsecal  flora  of  nurslings  and  bottle-fed 
children,  and  deserve  mention.  If  one  allows  faecal 
matter  from  a  normal  nursling  to  stand  in  a  thermostat 
in  a  closed  test-tube,  the  original  not  disagreeable  odor 
lasts  for  days  or  even  weeks,  although  the  material  as  a 
rule  contains  small  numbers  of  true  putrefactive  bacteria. 
Indeed,  it  is  possible  to  inoculate  such  normal  material 


14        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

with  Bienstock's  B.  putrijicus  quite  richly  without  any 
evidence  of  putrefaction,  although  the  organisms  are 
kept  under  anaerobic  conditions.  Although  this  observa- 
tion points  to  the  absence  of  putrefactive  processes, 
it  must  be  remembered  that  the  growth  of  anaerobes  is 
relatively  difficult  where  the  quantity  of  moisture  is 
limited,  as  in  the  case  of  the  foregoing  experiments,  and 
also  that  the  quantity  of  nutrient  material  available 
for  the  growth  of  putrefactive  anaerobes  is  small  in  the 
movements  of  normal  milk-fed  children.  A  similar 
result  is  obtainable  after  inoculating  concentrated 
fseces-agar  with  various  bacteria,  such  as  pyocyaneus, 
prodigiosus,  the  bacillus  of  Friedlander,  the  vibrio  of 
Metchnikoff,  and  various  strains  of  the  typhoid  bacillus. 
That  is  to  say,  such  f seces-agar  richly  inoculated  with  the 
foregoing  organisms  fails  to  show  any  growth,  whether 
the  acid  reaction  of  the  medium  be  retained  or  whether 
neutralization  has  taken  place.  On  the  other  hand,  it 
has  been  noted  that  B.  coli,  B.  fluorescens,  Staphylococcus 
intestinaliSj  streptococcus,  proteus,  and  the  paracolon 
organisms,  as  well  as  putrificus  are  apt  to  grow  some- 
what better.  From  this  observation  one  may  perhaps 
reach  the  conclusion  that  the  bacteria  of  the  intestinal 
tract  possess  an  elective  antagonistic  action  against 
foreign  types  of  microorganisms. 

An  effort  has  been  made  to  obtain  an  adequate  ex- 
planation for  this  behavior,  and  especially  to  determine 
whether  the  inhibition  for  bacteria  here  noted  depends 
on  the  production  of  definite  bactericidal  substances. 
The  methods  employed  by  Moro  and  Murath  were 


INFECTIONS  OF  THE  DIGESTIVE  TRACT        15 

similar  to  those  of  Conradi  and  Kurpjuweit.1  In  the 
series  of  observations  made  by  them  the  growth  of  the 
following  organisms  was  observed  on  the  specially  pre- 
pared plates :  B.  coli  communis,  B.  lactis  aerogenes, 
B.  typhi,  B.  Shiga-Kruse,  B.  Flexneri,  Staphylococcus 
pyogenes  aureus,  Diplococcus  intestinalis,  Soor,  B. 
prodigiosus,  and  B.  pyocyaneus.  The  results  were  by 
no  means  uniform,  but  showed  that  the  normal  nursling's 
stool  exerts  an  intense  inhibitory  action  against  various 
bacteria.  For  example,  B.  typhi  and  B.  Kruse  failed  to 
grow  even  in  dilutions  of  1 :  400.  On  the  other  hand,  the 
representatives  of  the  obligate  bacteria  of  the  intestine, 

1  One  volume  of  the  fresh  faeces  is  diluted  with  nine  volumes 
of  bouillon.  In  order  to  measure  the  fasces  one  may  use  a  glass 
capsule  of  1  c.c.  capacity,  which  is  then  emptied  by  means  of  a 
glass  rod  of  suitable  size,  into  the  bouillon.  Various  quantities 
of  the  yellowish  emulsion  are  now  permitted  to  flow  into  test 
tubes  containing  agar  cooled  to  42°  C.,  so  that  the  fluids  so  obtained 
represent  dilutions  of  TV,  £s,  -fa,  T£<T»  von,  and  T&T  of  the  original 
fsBcal  material.  After  thorough  mixing,  the  agar  is  plated  in 
Petri  dishes.  The  surface  of  these  plates  is  then  promptly  inocu- 
lated with  approximately  the  same  numbers  of  different  kinds 
of  bacteria. 

The  material  to  be  inoculated  is  prepared  by  inoculating  one 
normal  platinum  loop  of  a  twenty-four-hour  agar  culture  into 
10  c.c.  of  bouillon,  and  emulsifying  it.  From  this  emulsion  of 
bacteria  a  smaller  loopful  is  smeared  upon  the  surface  of  the  agar 
plates.  It  is  convenient  to  divide  up  the  agar  into  half  a  dozen 
regions  by  means  of  a  platinum  needle.  The  surface  of  each  one 
of  these  islands  may  be  smeared  with  a  different  culture  of  bac- 
teria so  that  the  growth  of  several  different  types  of  organisms 
may  be  observed  on  one  plate.  The  bacteria  inoculated  on  one 
of  these  islands  does  not  extend  to  others.  The  growth  is  observed 
at  the  end  of  twenty  to  twenty-four  hours,  and  controls  are  made 
with  material  of  the  same  origin,  diluted  to  one- tenth,  boiled,  and 
then  incubated  for  twenty-four  hours. 


16        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

B.  coli  communis  and  B.  lactis  aerogenes,  usually  grew 
fairly  well  and  suffered  little  inhibition.  This  was  a 
regular  occurrence  throughout  the  experiments.  Indeed, 
the  phenomenon  occurred  so  regularly  that  it  was  em- 
ployed as  the  basis  for  distinguishing  between  typhoid 
bacilli  and  colon  bacilli.  In  the  case  of  Staphylococcus 
pyogenes,  which  is  found  in  every  nursling's  stool,  there 
is  observed  very  little  inhibitory  action.  In  the  case 
of  B.  pyocyaneus  it  was  found  that  even  in  such  strong 
concentrations  as  1 : 10  there  was  good  growth  with  the 
production  of  pigment..  It  appears,  therefore,  that  in 
this  case  the  medium  favored  the  growth  of  pyocyaneus 
to  a  certain  extent.  The  dysentery  bacillus  of  Flexner 
in  some  cases  behaved  like  the  typhoid  bacillus,  but  in 
other  cases  showed  growth  in  a  dilution  of  1 : 100.  The 
action  of  this  medium  was  therefore  more  marked  upon 
the  whole  in  its  action  against  the  typhoid  bacillus  and 
the  Kruse  bacillus  than  against  the  Flexner  bacillus. 

The  Diplococcus  intestinalis,  a  constant  inhabitant  of 
the  nursling's  tract,  behaved  like  the  Staphylococcus 
pyogenes  in  developing  only  moderately.  The  growth 
of  the  thrush  organism  was  more  strongly  inhibited  than 
B.  prodigiosus.  The  development  of  color  was  checked 
on  all  the  plates  in  which  the  faecal  concentration  was 
fairly  strong. 

In  general,  the  inhibitory  substances  to  which  the 
restraining  effect  is  attributed  appeared  to  be  less  active 
in  the  fseces  of  the  nursling  than  in  those  of  grown 
persons. 

A  difference  between  the  inhibitory  action  of  the  fseces 


INFECTIONS  OF  THE  DIGESTIVE  TRACT        17 

of  nurslings  and  of  bottle-fed  children  could  not  be 
observed.  In  the  case  of  a  child  suffering  from  a  chronic 
catarrhal  condition  of  the  gastro-enteric  tract  and 
marasmus,  a  great  diminution  in  the  inhibitory  action 
was  observed.  It  seems  possible  that  this  might  be  inter- 
preted on  the  basis  of  a  diminished  growth  of  colon 
bacilli  rather  than  by  the  production  of  inhibitory 
substances. 

Experiments  made  with  meconium  showed  that  this 
material  held  no  bactericidal  substances.  On  the 
contrary,  when  mixed  with  agar  it  became  an  excellent 
nutrient  medium  for  bacteria,  although  by  itself  it  is 
only  a  poor  medium  for  most  varieties. 

It  is  interesting  to  observe  that  B.  bifidus,  which  forms 
the  chief  representative  of  the  nursling's  flora,  appeared 
to  be  unable  to  make  these  inhibitory  substances.  The 
question  arises  in  the  mind  of  the  critic  in  connection 
with  this  experiment,  whether  in  the  observations  re- 
ported there  was  in  reality  a  good  growth  of  B.  bifidus, 
which  is  an  organism  not  easily  cultivated  on  ordinary 
media. 

Moro  and  Murath  attribute  the  inhibitory  action  of  the 
nursling's  fseces  entirely  to  the  presence  of  organisms 
of  the  B.  coli  type.  A  comparison  of  typhoid  bacillus 
with  the  colon  bacillus  with  respect  to  the  ability  to 
inhibit  the  growth  of  various  microorganisms  showed 
that  the  typhoid  bacillus  possesses  little  or  no  capacity 
to  effect  this  inhibition. 

Criticism  of  Experiments  of  Conradi  and  Kurpjuweit.  — 
The  interpretation  to  be  placed  on  the  phenomenon  of 


18        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

inhibition  described  by  Conradi  and  Kurpjuweit  and  by 
Moro  and  Murath  is  not  yet  entirely  clear.  That  the 
observed  inhibition  is  due  to  complex  cellular  products  — 
the  "  autotoxines "  of  Conradi  —  is  questionable  in  view 
of  the  studies  of  Manteufel,1  of  Passini,2  and  of  Oebius.3 
Manteufel  showed  that  in  many  cases  where  the  surface 
of  a  plate  indicated  no  growth  on  inspection,  and  where 
consequently  it  would  be  assumed  that  an  inhibitory 
effect  had  been  exerted,  in  reality  many  small  micro- 
scopical colonies  were  present.  In  other  words,  the 
character  of  the  growth  may  be  of  such  a  nature  as  to 
mislead  one  into  the  belief  that  inhibition  has  occurred 
where  in  reality  such  inhibition  is  absent  or  slighter  than 
has  been  supposed.  In  these  cases  the  size  of  the  in- 
dividual surface  colonies  was  smaller  but  their  number 
was  increased  and  the  surface  could  certainly  not  be 
regarded  as  sterile.  Further  observations  made  it  very 
probable  that  the  exhaustion  of  the  culture  medium 
incidental  to  the  growth  of  the  faecal  flora  is  in  part  the 
cause  of  the  failure  of  the  surface  colonies  to  grow. 
The  assumption  that  there  are  produced  in  the  bouillon 
culture  thermolabile,  unfilterable,  and  dialyzable  sub- 
stances which  check  the  growth,  appears  unwarranted  in 
the  light  of  certain  experiments  with  reference  to  this 

1  "Untersuchungen  iiber  die  'Autotoxine'  (Conradi)  und  ihre 
Bedeutung  als  Ursache  der  Wachstumshemmung  in  Bakterien- 
kulturen,"  Berl.  klin.  Wochenschr.,  xliii,  p.  313,  1906. 

2  "Die  bakteriellen  Hemmungsstoffe  Conradis  und  ihr  Einfluss 
auf  das  Wachstum   der   Anaerobier  des   Darms,"    Wien.    klin. 
Wochenschr.,  xix,  p.  627, 1906. 

3 "  Ueber   spontane   Wachstumshemmung   der   Bakterien   auf 
kiinstlichen  Nahrboden,"  Med.  Klinik,  ii,  p.  598,  1906. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT        19 

point.  It  also  appears  doubtful  whether  there  are  heat- 
resisting  substances  formed  by  B.  coli  which  are  of  value 
in  checking  surface  growths  made  under  the  conditions 
already  mentioned.  It  was  found  that  there  was  no 
difference  in  the  surface  growth  of  B.  coli  if  the  agar  me- 
dium containing  twenty-four-hour  cultures  of  B.  coli  was 
heated  for  thirty  minutes  at  90°  C.  or  100°  C.  Of  course 
in  this  experiment  it  was  necessary  to  exclude  the  factor 
of  an  exhausted  medium  previous  to  making  the  surface 
cultures,  since  in  the  presence  of  such  an  exhausted 
medium  organisms  would  naturally  not  grow  upon  the 
surface.  These  various  experiments  speak  against 
any  specific  inhibitory  substances.  It  would,  indeed, 
be  a  remarkable  and  apparently  contradictory  phenom- 
enon if  organisms  should  form  substances  in  the  course 
of  their  growth  which  are  more  injurious  to  themselves 
and  their  own  species  than  to  foreign  ones.  Yet  this 
view  is  apparently  assumed  by  Conradi  to  be  correct. 
In  order  to  explain  the  dominance  of  the  colon  bacilli 
in  the  intestine  he  has  had  to  make  the  assumption  that 
these  organisms  have  given  rise  to  substances  against 
which  they  have  become  immunized  —  a  complex 
assumption.  It  is  also  singular  that  the  autotoxines 
of  Conradi  should  act  in  an  inhibitory  manner  without 
causing  actual  death,  if  it  be  true,  as  claimed,  that  these 
autotoxines  are  inhibitory  in  an  even  higher  degree  than 
carbonic  acid.  Conradi  and  Kurpjuweit,  in  spite  of  this 
fact,  attribute  the  bactericidal  action  of  fresh  faeces  to 
these  inhibitory  substances.  It  is  difficult  to  under- 
stand how,  if  these  supposed  restraining  substances  are 


20        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

really  only  inhibitory  and  not  bactericidal,  leaving  the 
bacteria  still  capable  of  growth  when  brought  into  better 
nutrient  media,  so  many  of  the  bacteria  in  the  fseces 
have  been  killed.  The  proof  remains  to  be  furnished 
that  the  death  of  these  bacteria  in  the  lower  part  of  the 
intestinal  tract  and  the  inhibition  at  higher  levels  are 
due  to  the  same  cause. 

It  is  only  fair  to  say  that  Conradi  and  Kurpjuweit 
have  not  succeeded  in  establishing  their  contention  that 
the  inhibitory  action  of  colon  bacilli  is  due  to  specific 
toxines  which  they  form.  The  inhibitory  action  de- 
scribed by  them  is  certainly  due  in  part  to  the  exhaustion 
of  the  media  by  the  freely  growing  colon  bacilli  and  in 
part  to  the  production  of  acid,  indol,  phenol,  or  other  pu- 
trefactive or  fermentative  substances.  It  would  be  going 
too  far,  however,  to  deny  that  substances  at  present 
unknown  to  us  may  possibly  have  a  part  in  bringing 
about  the  phenomena  of  inhibition. 

It  is  clear  that  the  colon  bacilli  can  act  protectively 
to  the  digestive  tract  only  when  they  are  able  to  grow 
freely.  If  the  conditions  are  such  in  the  tract  that  they 
cannot  multiply  abundantly,  they  can  neither  exhaust 
the  nutritive  materials  on  which  other  races  grow  nor 
make  products  endowed  with  inhibitory  powers.  There 
are  many  examples  of  disease  in  which  the  colon  bacilli 
disappear  not  merely  from  the  faeces,  but  from  the 
diarrhceal  stools.  Other  races  take  their  place.  This 
condition  is  quite  unintelligible  unless  we  assume  that 
the  colon  bacilli  no  longer  find  a  suitable  nutrient  medium 
in  the  mixture  of  digestive  juices  and  food.  Without 


INFECTIONS  OF  THE  DIGESTIVE  TRACT        21 

radical  changes  in  the  character  of  the  food  the  colon 
bacilli  have  in  many  instances  been  observed  to  resume 
their  prominent  position  in  the  intestinal  contents.  It 
is  reasonable  to  believe  that  the  return  of  more  normal 
secretory  conditions  in  the  digestive  tract  is  a  very 
influential  factor  in  determining  the  reinstatement  of 
the  legitimate  flora.  If  this  be  true,  the  therapeutic 
value  of  introducing  colon  bacilli  into  the  intestine 
(with  food  or  by  high  colon  injection)  with  a  view  to 
utilizing  their  restraining  action  upon  injurious  races 
must  be  less  than  would  at  first  sight  appear  to  be  the 
case.  There  is  need  for  much  careful  research  in  regard 
to  this  question. 

Influence  of  Reaction  on  the  Growth  and  Products  of 
Intestinal  Anaerobes.  —  If  mixed  faecal  flora  be  grown 
in  sugar  bouillon  and  in  sugar  bouillon  containing 
calcium  carbonate  for  one  week  at  37°  C.,  it  will  be  found 
that  a  considerable  amount  of  volatile  fatty  acids  has 
been  formed  in  each  case.  The  quantity  will  usually 
be  found  to  be  greater,  often  considerably  greater,  in  the 
flask  containing  calcium  carbonate  than  in  the  flask  with- 
out it.  Similar  results  are  obtained  if  one  substitutes 
magnesium  carbonate  for  the  calcium  salt.  The  observed 
difference  in  the  quantity  of  acids  is  therefore  probably 
not  due  to  a  specific  effect  of  the  calcium  salt,  but  to  its 
action  in  maintaining  a  neutral  reaction. 

In  a  series  of  observations  of  the  sort  just  mentioned, 
which  were  carried  out  by  Dr.  A.  J.  Wakeman,  two  things 
are  worthy  of  note.  First,  it  was  found  that  in  nearly 
all  instances  the  molecular  weights  of  the  volatile  fatty 


22        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

acids  were  at  least  somewhat  higher  in  the  case  of  the 
cultures  in  the  sugar-bouillon-carbonate  media  than 
in  the  corresponding  growths  in  sugar  bouillon.  This 
fact  suggests  a  relatively  greater  activity  of  putrefactive 
bacteria  in  the  neutral  media,  for  it  is  known  that  such 
bacteria  tend  to  form  the  higher  rather  than  the  lower 
volatile  fatty  acids.  This  view  was  confirmed  by  the 
study  of  the  bacteria  dominant  in  the  two  series  of  flasks. 
Secondly,  it  was  found  by  Dr.  Wakeman  that  in  almost 
every  instance  the  proportion  of  non-volatile  acids 
(mainly  lactic)  was  greater  in  the  sugar-bouillon  cultures 
than  in  the  neutralized  cultures.  The  most  reasonable 
interpretation  of  these  results  is  that  a  neutral  medium 
favors  the  development  of  putrefactive  bacteria  (especi- 
ally of  the  anaerobes),  whereas  an  acid  medium  (such  as 
is  maintained  in  the  sugar-bouillon  flasks)  restrains  the 
growth  of  these  bacteria  and  favors  the  growth  of  the 
lactic  acid  makers.  It  is  probable  that  in  the  case  of 
the  neutral  flasks  some  of  the  lactic  acid  formed  is  con- 
verted into  butyric  acid. 

These  observations  and  similar  ones  with  pure  cultures 
indicate  that  in  the  digestive  tract  the  growth  of  putre- 
factive anaerobes  must  be  favored  by  a  neutral  reaction 
and  restrained  by  the  presence  of  acid.  The  favorable 
influence  of  milk  food,  containing  lactic-acid  formers, 
in  controlling  putrefactive  decompositions  in  the  digest- 
ive tract  finds  its  explanation  partly  in  the  inhibitory 
action  exerted  by  such  bacteria  and  in  part  in  the 
presence  of  preformed  lactic  acid  in  the  food  at  the 
time  it  is  ingested. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT        23 

AEROBIC  AND   ANAEROBIC   CONDITIONS   IN   THE 
DIGESTIVE    TRACT 

There  are  many  conditions  which  influence  the  char- 
acter and  extent  of  bacterial  decompositions  in  the  ali- 
mentary tract.  The  chemical  character  of  the  food 
(quite  aside  from  the  bacteria  it  may  contain) ,  the 
solubility  of  the  food  in  the  digestive  juices,  the  volume 
and  composition  of  these  digestive  juices,  all  affect  in 
important  ways  the  ultimate  fate  of  the  food  in  its 
relation  to  microorganic  decomposition.  Some  phases 
of  these  influences  will  be  discussed  in  these  pages  in 
connection  with  special  problems,  although  it  must 
be  owned  that  our  knowledge  of  them  is  far  from  being 
full,  owing  partly  to  the  great  difficulties  of  experi- 
mental investigation.  Intimately  intermingled  with 
these  factors  of  food  and  secretory  activity  is  the  influ- 
ence of  aerobic  and  anaerobic  conditions  in  the  digestive 
tract  upon  the  nature  of  the  bacterial  activities  that 
occur  there. 

Pasteur,  with  his  sharp  insight  into  biological  phe- 
nomena, was  first  in  recognizing  the  ability  of  certain 
microorganisms  (including  a  butyric  acid  producer, 
yeast  plants,  aspergillus,  and  some  mucors)  to  live  in  the 
absence  of  oxygen  and  thereby  first  to  distinguish  be- 
tween aerobic  and  anaerobic  life.  He  embodied  his  views 
in  a  famous  epigram,  the  validity  of  which  has  been  much 
discussed  — "  Fermentation  is  life  without  oxygen." 
This  statement,  although  too  sweeping  and  exclusive, 
has  in  it  a  large  element  of  truth  and  has  a  special 


24        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

significance  in  its  application  to  the  bacterial  processes 
in  the  digestive  tract.  This  significance  comes  from  two 
fundamentally  important  facts :  first,  that  the  initiation 
of  putrefactive  decompositions  in  the  digestive  tract 
(as  elsewhere)  depends  very  largely,  though  probably 
not  exclusively,  on  the  activities  of  obligate  anaerobes ; 
secondly,  that  an  important  portion  of  the  digestive 
tract  is  most  of  the  time  under  anaerobic  conditions. 
The  importance  of  the  role  taken  by  obligate  anaerobes 
in  bringing  about  putrefactive  decomposition  in  native 
proteids  is  only  beginning  to  be  appreciated.  Bien- 
stock  *  made  an  important  contribution  to  biology  when 
on  definite  experimental  evidence  he  insisted  on  the 
inability  of  the  ordinary  facultative  anaerobes  to  attack 
native  proteids,  and  showed  that  obligate  and  strict 
anaerobes  like  B.  putrificus  are  able,  quite  unaided,  to 
break  down  proteids.  Dr.  Rettger,2  in  his  numerous 
experiments  on  putrefactive  decomposition,  confirmed 
and  extended  the  work  of  Bienstock.  He  showed  that 
an  egg-meat  mixture  is  not  attacked  by  B.  lactis  aerogenes, 
B.  coll.  Streptococcus  pyogenes,  B.  alcaligenes  fcetidus, 
proteus  vulgaris,  etc.,  whereas  it  is  regularly  decomposed 
by  strict  anaerobes  such  as  B.  putrificus,  B.  maligni 
cedematis,  and  B.  anthracis  symptomatici  (bacillus  of 
quarter-evil).  This  is  a  severe  test,  and  there  are  putre- 
factive anaerobes  which  cannot  attack  the  egg-meat 


1  "  Untersuchungen  iiber  die   Aetiologie   der   Eiweissfaulnis," 
Archiv  /.  Hyg.,  xxxvi,  p.  335,  1899;  ibid.,  xxix,  p.  390,  1900. 

2  "Studies  on  Putrefaction,"   Journ.  of  Biol.  Chem.,  ii,  p.  71, 
1906. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT        25 

mixture  but  which  are  nevertheless  intensely  putre- 
factive when  grown  in  a  medium  containing  a  low  per- 
centage of  sugars  as  well  as  native  proteids.  This  is 
true  of  B.  aerogenes  capsulatus.  I  can  confirm  the  obser- 
vation that  B.  coli  cannot  decompose  media  consisting 
of  native  proteids  even  on  long  standing.  On  the  other 
hand,  there  is  no  more  striking  type  of  putrefaction  than 
that  induced  in  proteids  by  B.  putrificus  upon  egg-meat 
mixture. 

At  the  present  time  I  know  of  no  evidence  to  show 
that  native  proteids  can  be  actively  decomposed  by  any 
of  the  ordinary  facultative  anaerobes,  and  in  respect  to 
the  digestive  tract  the  facts  all  point  to  the  correctness 
of  the  view  that  we  largely  owe  the  initiation  of  proteid 
cleavage  there  to  the  agency  of  the  strict  anaerobes. 
But  it  must  be  remarked  in  passing  that  it  does  not 
follow  from  what  has  just  been  said  that  intestinal 
putrefaction  is  carried  on  through  the  sole  activity  of 
strict  anaerobes.  The  fact  that  these  organisms  are  the 
great  destroyers  of  native  proteids  does  not  tell  the 
story  of  the  entire  putrefactive  process.  The  intestine 
abounds  with  microorganisms  which  are  able  to  attack 
albumoses  and  peptones  and  to  effect  a  further  degra- 
dation of  the  proteid  molecule,  thus  entering  into  a 
symbiotic  action  with  the  strict  anaerobes. 

It  appears  desirable  to  state  at  this  point  just  what  is 
meant  by  the  expression  " anaerobic  life'7  as  applied  to 
the  strict  anaerobes  to  which  reference  has  been  made. 
When  we  speak  of  anaerobic  life,  we  are  liable  to  vaguely 
picture  a  state  of  existence  in  which  the  microorganisms 


26        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

concerned  are  subsisting  without  access  to  any  oxygen 
whatsoever,  and  the  term  "strict  anaerobe"  tends  to 
give  fixity  to  such  a  conception.  Such  an  idea,  however, 
would  be  far  from  expressing  the  actual  truth,  since  there 
is  no  known  exception  to  the  rule  that  living  microorgan- 
isms cannot  maintain  themselves  without  producing 
carbon  dioxide,  a  process  which  involves  the  oxidation 
of  organic  materials  within  the  cell.  But  the  quantity 
of  oxygen  required  to  maintain  life  may  be  extremely 
small,  and  it  is  in  this  sense  only — which  is  expressed  in 
the  term  "micro-aerophile,"  suggested  by  Beijerinck1  — 
that  we  are  justified  in  speaking  of  anaerobic  micro- 
organisms. It  has  been  calculated  by  Matzushita2 
that  anaerobes  may  live  although  the  surrounding  air 
contains  not  more  than  0.0031  per  cent,  of  oxygen. 
This  fact  is  liable  to  mislead  us  if  we  accept  it  as  meaning 
more  than  that  the  presence  of  very  little  oxygen  in 
the  air  is  consistent  with  the  maintenance  of  some 
forms  of  microorganic  life.  For,  on  the  one  hand,  it 
seems  clear  that  microorganisms  may  obtain  their  small 
portion  of  essential  oxygen  not  from  the  air,  but  from 
a  medium  containing  a  decomposable  substance  which, 
like  glucose,  contains  oxygen  which  becomes  available 
for  the  support  of  life.  In  other  conditions  the  body  of 
the  microorganism  may  contain  material  which  is  capable 
of  yielding  oxygen  for  a  time,  in  minute  amounts. 

1  Arch.  Norland,  ii,  1899. 

2"Zur  Physiologic  der  Sporenbildung  der  Bacillen,  nebst 
Bemerkungen  zum  Wachstum  einiger  Anaeroben,"  Archiv  /.  Hyg., 
xliii,  p.  327,  1902. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT        27 

It  is  conceivable  that  under  such  conditions  as  those 
just  mentioned,  it  becomes  a  matter  of  indifference  to 
the  anaerobes  how  little  oxygen  is  contained  in  the  sur- 
rounding air.  On  the  other  hand,  it  is  well  known  that, 
paradoxical  as  it  seems,  the  strictest  anaerobes  known 
are  able  to  grow  freely  in  apparently  close  contact  with 
a  fairly  abundant  supply  of  oxygen,  provided  aerobic 
bacteria  are  also  present.  Pasteur,  to  whom  this  note- 
worthy symbiotic  phenomenon  was  known,  ascribed  it 
to  the  circumstance  that  the  aerobes  remove  the  oxygen 
present  in  so  thorough  a  way  that  the  anaerobes  are 
unhindered  in  their  growth.  This  doctrine,  which 
found  wide  acceptance,  has  lately  been  questioned  by 
Kedrowski  *  (and  others),  who  attribute  the  ability  of 
anaerobes  to  grow  symbiotically  with  aerobes  to  the 
formation  of  a  "ferment"  by  the  latter,  which  renders 
the  anaerobes  immune  to  the  action  of  oxygen.  It 
cannot  be  said  that  this  hypothesis  has  received  sub- 
stantial support,  and  we  are  compelled  to  return  to  the 
teaching  of  Pasteur  or  to  some  modification  of  it.2  There 
is  a  limit  to  the  amount  of  oxygen  which  the  aerobes 

1  "  Ueber  die  Bedingungen  unter  welchen  anaerobe  Bakterien 
auch  bei  Gegenwort  von  Sauerstoff  existiren  konnen,"  Zeitschr. 
f.  Hyg.,  xx,  p.  358,  1896. 

2  See    Walter    von    Oettingen,    "Anaerobic    iind    Symbiose," 
Zeitschr.  /.  Hyg.,  xliii,  p.  475,  1903.     This  writer  contends  that 
the  primary  action  in  aerobic  and  anaerobic  symbiosis  is  the  split- 
ting action  of  the  anaerobes  in  sugar  with  their  associated  inability 
to  appropriate  the  oxygen  contained  in  carbohydrates,  that  oxy- 
gen being  eagerly  seized  by  the  aerobes  for  their  use.     It  is  hard  to 
reconcile  this  view  with  the  retarded  growth  of  the  anaerobes  (as 
compared  with  the  aerobes)  in  some  symbiotic  experiments.     In 
this  paper  will  be  found  the  literature  on  the  subject. 


28        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

can  divert  from  the  anaerobes,  and  it  is  easy  to  check 
the  growth  of  anaerobes  which  are  not  facultative  by 
passing  oxygen  with  some  freedom  through  the  fluid 
medium,  no  matter  how  many  aerobes  are  present. 

A  study  lately  made  by  Willimsky  *  on  the  adaptation 
of  aerobic  bacteria  to  anaerobic  conditions  shows  that 
aerobic  bacteria  like  the  spirillum  of  cholera,  B.  alkali- 
genes,  B.  fluorescens  non  liquefaciens,  are  able  to  adapt 
themselves  to  an  atmosphere  in  which  there  remains 
only  a  minimal  trace  of  oxygen  and  that  this  adapta- 
tion is  the  more  efficient  the  more  slowly  the  oxygen  is 
withdrawn,  sudden  withdrawal  of  oxygen  greatly  slowing 
the  multiplication  of  the  organisms.  The  multiplication 
of  organisms  was  found,  however,  to  be  much  less  rapid 
where  oxygen  had  been  thus  withdrawn  than  where  it 
is  present.  When  an  absolutely  anaerobic  condition  was 
brought  about,  the  organisms  died,  and  their  destruction 
was  the  more  rapid,  the  more  abrupt  the  withdrawal  of 
oxygen. 

The  symbiosis  of  aerobes  and  anaerobes  is  a  biological 
phenomenon  of  much  consequence  in  determining  the 
distribution  of  anaerobic  bacterial  processes  in  the  diges- 
tive tract.  Without  such  symbiotic  action  the  develop- 
ment of  strict  anaerobes  would  be  confined  to  those  parts 
of  the  digestive  tract  into  which  oxygen  rarely  passes, 
and  then  only  in  small  amounts.  The  large  intestine 
is  seldom  visited  by  free  oxygen,  but  it  is  probably 
usual  in  man  for  the  small  intestine  to  contain  a  little 

1  "Ueber  des  Verhalten  der  aeroben  Keime  gegeniiber  der  ab- 
soluten  Sauerstoffentziehung,"  Archiv  f.  Hyg.,  liv,  p.  375,  1905. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT        29 

air.  Boycott  *  in  his  observations  on  the  gases  of  the 
intestine  found  that  the  small  intestine  of  the  cat  gener- 
ally contains  a  little  oxygen,  while  the  large  intestine 
holds  either  no  oxygen  or  a  smaller  percentage  than  is 
present  in  the  small  intestine.  Sometimes  the  proportion 
of  oxygen  in  the  gas  from  the  large  intestine  was  a  little 
above  one  part  per  hundred.  Boycott  noticed  that  oxy- 
gen passes  very  readily  out  of  the  intestine,  partly 
by  diffusion,  but  mainly  by  being  appropriated  by  the 
mucous  membrane.  There  is  apparently  very  little 
direct  exchange  with  the  blood.  In  the  stomach  and 
cavity  of  the  mouth  there  is  always  a  considerable 
quantity  of  oxygen  —  unless,  indeed,  the  oxygen  in  the 
stomach  be  displaced  by  the  development  of  an  abundance 
of  carbon  dioxide,  as  sometimes  happens.  It  is  probably 
safe  to  assume  that  in  the  mouth  the  free  presence 
of  oxygen  constantly  acts  as  a  deterrent  to  anaerobic 
growth.  In  spite  of  this,  however,  anaerobic  life  is 
possible,  and  the  indications  are  accumulating  which 
point  to  the  important  part  played  by  anaerobes  in  setting 
up  pathological  states  in  the  mouth.  Caries  of  the  teeth, 
which  was  formerly  referred  to  aerobic  bacterial  action, 
seems  clearly  the  result  of  the  invasive  action  of  anae- 
robes on  the  tooth  pulp.  In  certain  derangements  of 
digestion,  I  have  noticed  that  butyric  acid  fermentation 
or  putrefaction  takes  place  with  great  rapidity  in  the 
food  particles  that  have  lodged  between  the  teeth,  espe- 
cially if  carbohydrate  food  has  been  taken.  It  must  be 

1  "  Observations  on  the  Gaseous  Metabolism  of  the  Small  In- 
testine of  the  Rabbit,"  Journ.  of  Physiol.,  xxxii,  p.  343,  1904-05. 


30        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

admitted  that  proof  is  wan  ting  that  butyric  acid  formation 
in  the  mouth  is  always  due  to  anaerobes.  The  growth  of 
anaerobes  in  the  mouth  is  favored  by  want  of  cleanliness 
there,  since  the  accumulation  of  food-masses  encour- 
ages anaerobic  conditions  beneath  the  surface.  Probably 
the  intelligent  and  free  use  of  the  tooth-brush  is  a  most 
potent  means  of  discouraging  anaerobic  growth  in  the 
mouth.  In  removing  decomposing  food-masses  one 
not  merely  admits  air  to  the  anaerobes,  but  also  removes 
many  aerobes  which,  through  the  symbiotic  action 
already  mentioned,  facilitate  the  multiplication  of  the 
former. 

In  the  normal  human  stomach  the  conditions  for  the 
development  of  anaerobic  bacteria  are  usually  poor, 
partly  on  account  of  the  presence  of  air,  but  mainly 
owing  to  the  action  of  the  gastric  juice.  Nevertheless 
the  interior  of  a  food  bolus  must  often  afford  good 
opportunities  for  the  growth  of  anaerobes  that  happen 
to  be  taken  with  the  food.  In  a  stomach  which  secretes 
little  or  no  hydrochloric  acid,  and  which  is  sluggish  in 
emptying  its  contents,  the  chances  for  anaerobic  develop- 
ment are  good,  and  hence  we  frequently  find,  under  these 
circumstances,  that  there  are  evidences  of  putrefactive 
decomposition  of  food  that  has  been  unduly  retained 
in  the  stomach  (e.g.  production  of  sulphuretted  hydro- 
gen, mercaptan,  butyric  acid,  etc.).  Sometimes,  too, 
we  have  definite  infections  of  the  stomach  wall  with  bac- 
teria which  are  facultative  anaerobes  (e.g.  streptococci), 
and  which  are  capable  of  inducing  acute  lesions  of  the 
stomach.  On  the  whole,  however,  I  think  one  may  say 


INFECTIONS  OF  THE  DIGESTIVE  TRACT        31 

that  in  the  course  of  chronic  gastric  affections,  the 
number  of  anaerobic  microorganisms  in  the  stomach  is 
seldom  great. 

We  are  able  to  form  an  opinion  as  to  the  bacterial  con- 
ditions that  prevail  in  the  stomach  because  this  organ  is 
readily  accessible  through  the  aid  of  the  stomach-tube. 
Of  the  conditions  of  bacterial  life  in  the  small  intestine 
we  know  really  very  little,  because  of  the  inaccessibility 
of  the  contents  of  this  portion  of  the  digestive  tract 
during  life.  It  is,  of  course,  well  established  that  the 
duodenum  and  jejunum  contain  few  bacteria  and  that 
these  are  usually  not  of  the  kind  that  produce  pathogenic 
effects  or  induce  putrefaction.  For  example,  Gushing 
and  Livingston  *  found  that  in  gunshot  wounds  of  the 
upper  part  of  the  small  intestine,  the  bacteria  which 
escaped  into  the  peritoneal  cavity  did  little  or  no  harm 
-a  result  in  sharp  contrast  with  what  happens  after 
injuries  at  lower  levels  of  the  digestive  tract.  Again,  if 
we  take  the  intestinal  contents  from  the  jejunal  or  duo- 
denal level  of  the  gut  of  a  person  recently  dead  of  an 
acute  disease  not  especially  implicating  the  digestive 
tract  (e.g.  pneumonia),  it  will  be  found  that  the  bacteria, 
while  acting  readily  on  sugars,  owing  to  the  presence  of 
B.  lactis  aerogenes,  do  not  induce  putrefactive  decompo- 
sition on  proteid  media.  There  are  exceptions  to  this 

1  "  Experimental  and  Surgical  Notes  upon  the  Bacteriology  of 
the  Upper  Portion  of  the  Alimentary  Canal,  with  Observations 
on  the  Establishment  there  of  an  Amicrobic  State  as  a  Preliminary 
to  the  Operative  Procedures  on  the  Stomach  and  Small  Intestine," 
"Contributions  to  the  Science  of  Medicine  by  the  pupils  of 
William  Welch,"  p.  543,  1900. 


32        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

rule,  but  they  do  not  alter  the  general  applicability  of  the 
statement  that  putrefactive  microorganisms  are  com- 
monly few  in  the  upper  two  thirds  of  the  small  intestine. 
The  chief  factors  in  bringing  about  this  state  of  relative 
freedom  from  anaerobic  organisms  are  apparently  the 
defensive  action  of  the  stomach  juices  and  the  rapid 
passage  of  the  chyme  through  the  upper  intestine,  which 
offers  little  chance  for  the  multiplication  of  anaerobes, 
or  indeed  of  bacteria  of  any  kind.  To  what  extent  the 
moderate  amount  of  oxygen  present  inhibits  bacterial 
growth  is  uncertain. 

In  the  human  ileum,  the  character  of  the  bacterial 
decompositions  in  healthy  persons  appears  to  differ 
rather  widely  according  to  a  variety  of  conditions,  some 
of  which  are  still  obscure.  Perhaps  on  account  of  the 
approach  to  the  ileocsecal  valve,  which  offers  some 
degree  of  mechanical  difficulty  to  the  passage  of  the  con- 
tents of  the  small  intestine,  there  is  an  accumulation  of 
bacteria  in  the  ileum.  This  mechanical  obstacle,  in  the 
human  intestine  and  in  that  of  many  lower  animals 
(e.g.  dog),  consists  partly  in  the  narrowing  of  the  lumen 
of  the  gut,  but  partly  also  in  the  presence  of  inspissated 
intestinal  contents  on  the  further  side  of  the  valve,  in 
the  colon  itself.  In  man  there  is  within  a  foot  or  two 
of  the  colon  a  marked  increase  in  the  number  of  bacteria 
in  the  ileum,  and  this  increase  relates  not  merely  to  the 
total  number  of  bacteria  present,  but  also  to  the  varieties. 
The  mere  accumulation  of  material  affords  opportunity 
for  anaerobic  conditions  of  life,  and  we  find  in  fact  that 
the  numbers  of  strict  anaerobes  in  the  lower  part  of  the 


INFECTIONS  OF  THE  DIGESTIVE  TRACT         33 

human  intestine  and  in  that  of  dogs  is  much  increased 
in  the  ileum  as  compared  with  higher  levels.  Hence 
we  find  that  the  mixed  faecal  bacteria  taken  from  this 
level  of  the  lower  ileum  are  capable  of  inducing  putre- 
factive changes  in  native  proteids  and  in  more  simple 
nitrogen-holding  media.  This  is  true  of  the  human  ileum 
in  health  and  at  all  periods  of  life,  but  the  accumulation 
of  putrefactive  bacteria  is  even  more  pronounced  in 
certain  cases  of  disease  —  in  other  words,  anaerobic  con- 
ditions of  bacterial  life  are  exaggerated  in  pathological 
states.  We  may  indeed  look  on  the  ileum  as  the  debat- 
able land  of  the  digestive  territory.  In  ideal  health 
this  region  contains  relatively  few  anaerobes  and  patho- 
genic bacteria;  in  acute  and  chronic  intestinal  patho- 
logical processes  the  ileum  is  probably  inhabited  by 
flora  capable  of  producing  substances  which  may 
damage  the  organism  either  locally  or  generally,  and 
among  these  the  anaerobes  are  apt  to  be  prominent. 

In  the  large  intestine  we  find  the  most  dense  accumu- 
lation of  bacteria  and  the  best  conditions  for  anaerobic 
growth.  The  transition  from  small  to  large  intestine 
is  in  this  respect  very  striking,  more  regularly  so,  per- 
haps, in  dogs  than  in  human  beings.  In  dogs  the  large 
intestine  is  usually  closely  crowded  with  bacteria  beyond 
the  ileocaBcal  valve,  whatever  may  be  the  conditions  in 
the  ileum.  The  anaerobic  conditions  are  well  main- 
tained throughout  the  large  intestine,  and  it  is  here  that 
we  find  the  greatest  numbers  of  anaerobes  and  the  most 
pronounced  evidence  of  putrefaction.  There  is,  however, 
a  gradual  fall  hi  the  number  of  living  bacteria  beyond  the 


34        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

ileocaecal  valve,  so  that  in  the  rectum  the  numbers  of  culti- 
vable bacteria  are  very  much  less  than  in  the  ascending 
colon.  But  although  in  the  ascending  colon  we  have  usu- 
ally the  greatest  numbers  of  bacteria,  it  should  be  noted 
that  their  variety  is  often  not  so  great  as  in  the  ileum. 

With  a  view  to  learning  something  about  the  anaerobic 
conditions  in  the  intestine,  and  their  relation  to  the  re- 
ducing power  of  bacteria,  a  number  of  experiments  were 
made  in  which  dogs  were  fed  on  meat  containing  methyl- 
ene  blue.1  The  animals  were  killed  and  the  contents  of 
the  intestine  examined  under  boiled  water  in  order  to 
determine  at  what  point  in  the  intestine  reduction  of 
methylene  blue  had  occurred.  The  following  typical 
result  was  obtained  in  one  instance.  A  dog  weighing 
fourteen  and  one-half  pounds  had  received  methylene 
blue  in  water,  about  two  hundred  milligrams  in  all. 
On  the  third  day  he  received  one  hundred  milligrams 
of  methylene  blue,  placed  inside  a  piece  of  cooked  meat. 
He  ate  heartily  of  this  meat  and  four  hours  after  the  meal 
the  animal  was  killed  and  the  intestine  examined. 
The  following  diagram  of  the  large  and  small  intestines 
indicates  the  points  at  which  the  contents  were  examined. 

SMALL  INTESTINE 


A 

B 

C 

D 

E 

F 

The  stomach  was  found  to  be  about  one-half  full,  and 
intensely  blue.    In  the  duodenum,  at  A,  the  intestinal 

1 1  am  indebted  to  Dr.  A.  J.  Wakeman  for  the  series  of  proto- 
cols on  which  these  statements  are  based. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT         35 

contents  were  intensely  blue,  the  color  diminishing  in 
intensity  toward  B  until  at  C  the  color  had  almost 
disappeared  and  had  entirely  disappeared  between  C 
and  D.  The  contents  of  the  intestine  obtained  from  D 
blued  only  when  exposed  to  air.  When  boiled  with 
hydrochloric  acid,  water,  and  hydrogen  peroxide,  they 
became  intensely  blue.  The  contents  of  the  colon 
(between  E  and  F)  were  not  blue  under  water,  but  be- 
came blue  very  quickly  when  exposed  to  air.  The 
mucus  adhering  to  the  mucous  membrane  of  the  intes- 
tinal tract  behaved  in  general  like  the  intestinal  contents 
as  regards  the  color.  This  experiment  indicates  that 
beyond  the  middle  of  the  small  intestine  the  conditions 
become  rapidly  anaerobic  or  very  nearly  so,  since  the 
reduction  of  methylene  blue  in  this  concentration  could 
not  occur  in  the  presence  of  the  air.  The  main  factors 
in  the  reduction  process  are,  of  course,  the  bacteria,  and 
it  is  noteworthy  that  the  reduction  of  the  methylene 
blue  begins  at  just  that  level  of  the  intestine  in  which 
the  bacteria  begin  to  be  numerous.  There  is  probably 
in  these  cases  not  merely  a  reduction  of  the  methylene 
blue,  but  decomposition  of  this  salt,  with  the  liberation 
of  hydrochloric  acid  and  the  production  of  the  methylene 
blue  leucobase.  This  is  indicated  by  the  behavior  of 
the  leuco-body  with  hydrochloric  acid. 

THE  BACTERIA  OF  THE  HUMAN  DIGESTIVE  TRACT  AT  DIF- 
FERENT AGES  IN  APPARENTLY  HEALTHY  INDIVIDUALS 

While  it  is  true  that  at  all  periods  of  life  the  human 
digestive  tract  is  the  seat  of  the  life  activities  of  myriads 


36         INFECTIONS  OF  THE  DIGESTIVE  TRACT 

of  microorganisms,  it  is  also  true  that  the  biological 
characters  of  these  microorganisms  are  not  the  same  at 
all  times  of  life.  If  we  compare  the  bacterial  flora  of 
apparently  healthy  persons  of  about  the  same  age;  we 
may  find  considerable  differences  in  those  parts  of 
the  digestive  tract  that  are  easily  accessible  to  study, 
and  yet,  upon  the  whole,  the  resemblances  in  the  bio- 
logical characters  of  the  bacteria  so  compared  will 
ordinarily  be  more  striking  than  the  differences,  pro- 
vided the  comparison  be  made  between  the  flora  of  in- 
dividuals living  in  a  temperate  climate  and  on  the  kind 
of  food  that  is  usual  in  countries  commonly  regarded  as 
civilized.  But  if  it  were  practicable  to  compare  the 
bacterial  flora  of  the  same  individual  at  different  periods 
of  life,  it  would  be  found  that  there  are  wide  and 
perhaps  characteristic  variations  —  variations  dependent 
in  part  on  differences  in  food,  but  in  part  on  other 
influences.  Such  comparisons  have  probably  seldom 
been  made  in  the  same  individual  over  a  long  period 
of  time,  but  comparisons  between  different  persons  of 
unequal  ages,  but  in  general  similarly  conditioned,  have 
been  repeatedly  made  and  support  the  statement  that 
the  normal  bacterial  flora  characteristic  of  different 
ages,  present  different  biological  characters  and  are 
responsible  for  different  types  of  decomposition  in  the 
digestive  tract. 


THE  BACTERIAL  PROCESSES  IN  THE  DIGEST- 
IVE TRACT  OF  NORMAL  NURSLINGS  AND 
BOTTLE-FED  INFANTS 

Nursling  Infants.  —  In  babies  fed  on  mother's  milk 
the  alimentary  tract  is  the  seat  of  conditions  of  bacterial 
activity  that  possess  a  high  degree  of  interest  for  one  who 
wishes  to  obtain  an  insight  into  the  physiology  of  diges- 
tion. For  in  nurslings  one  finds  a  relatively  simple  bac- 
terial flora  which  gives  a  clew  to  the  more  complex  and 
puzzling  bacterial  conditions  that  characterize  normal 
adult  life  and  many  states  of  disease.  The  healthy 
nursling's  bacterial  flora  is  not  merely  relatively  simple 
as  regards  the  varieties  of  microorganisms;  it  is  also 
remarkably  definite  in  the  individual  child  during  the 
nursling  period  as  well  as  in  different  children  who  are 
nourished  on  mother's  milk. 

By  means  of  the  Gram  stain,  carefully  employed,  it 
is  possible  to  divide  all  the  bacteria  present  at  a  given 
level  into  two  groups,  those  which  retain  the  stain  and 
thus  appear  dark  blue  in  the  microscopical  field  (Gram- 
positive  bacteria)  and  those  which  do  not  retain  the 
stain  (Gram-negative  bacteria),  and  are  hence  suscep- 
tible to  coloration  by  a  counter-stain  (a  red  dye  such 
as  fuchsin  or  saffranin  being  usually  chosen).  As  these 
different  ways  of  behaving  to  the  stain  correspond  to 
biochemical  peculiarities  of  the  bacteria,  we  have  at  our 

37 


38         INFECTIONS  OF  THE  DIGESTIVE  TRACT 

disposal  a  rough  means  of  differentiation  which  is  often 
of  great  service  in  the  microscopical  identification  (in 
so  far  as  this  is  possible)  of  bacterial  types.  If  this 
method  of  study  be  supplemented  by  making  aerobic  and 
anaerobic  cultures  on  gelatin  plates,  sugar-agar  plates, 
and  blood-agar  plates  (with  or  without  sugar),  one  ob- 
tains a  fair  idea  of  the  really  representative  bacteria 
present  in  the  alimentary  tract.  Some  of  the  bacteria 
present  may,  however,  fail  to  grow  on  any  of  these  media. 
Gram-stained  microscopical  fields  prepared  from  the 
normal  slightly  acid,  orange-yellow,  rather  soft  fa3ces  of 
a  nursling  child  from  any  portion  of  the  large  intestine, 
present  essentially  the  same  characteristic  appearances. 
In  the  first  place,  the  bacteria  are  seen  to  be  extremely 
abundant  —  more  so  than  in  the  f seces  of  normal  adults 
and  very  much  more  so  than  in  the  meconium.  A  very 
large  proportion  of  them  are  Gram-positive.  The 
great  majority  of  these  Gram-positive  bacteria  present 
the  same  appearances  and  may  give  to  a  field  the  appear- 
ance of  consisting  of  a  nearly  pure  culture  of  one  bac- 
terial type.  These  bacteria  are  slender,  often  slightly 
curved  bacilli  of  moderate  size.  They  constitute  the 
characteristic  microorganisms  of  the  human  nursling's 
digestive  tract  and  have  been  named  (for  reasons  which 
will  later  appear)  B.  bifidus  by  Tissier,  who  first  described 
them  and  took  them  out  of  the  group  of  colon  bacilli, 
with  which  they  had  been  grouped  by  Escherich. 
Mixed  in  with  B.bifidus  is  another  Gram-positive  bacillus, 
which  is  closely  related,  but  grows  readily  on  a  strongly 
acid  medium  and  has  hence  been  designated  B.  acidophi- 


INFECTIONS  OF  THE  DIGESTIVE  TRACT         39 

lus  (Moro).  These  bacilli  are  not  surely  distinguishable 
from  B.  bifidus  in  the  Gram-stained  field.  Although 
B.  bifidus  thus  dominates  the  typical  field,  other  Gram- 
positive  bacteria  can  always  be  found.  Of  these  the 
most  important  (though  very  few  in  number)  are  large, 
plump  bacilli,  occurring  usually  singly,  but  sometimes 
in  pairs.  This  is  the  B.  aerogenes  capsulatus  (B.  Welchii 
or  gas-phlegmon  bacillus  of  Fraenkel).  As  will  be  seen 
later,  it  may  play  an  important  part  in  the  pathology 
of  the  digestive  tract.  Another  Gram-positive  organism 
which  is  regularly  present  in  small  numbers  in  the  field 
is  a  diplococcus  which  frequently  grows  in  chains.  This 
coccus  is  commonly  associated  with  a  similar  organism 
which  is  Gram-negative.  The  chief  remaining  Gram- 
negative  bacteria  are  small  coccal  or  coccoid  forms  and 
shorter  and  longer  bacilli  which  by  cultural  methods 
can  be  shown  to  have  the  biological  characters  of  the 
B.  lactis  aerogenes  group  and  the  B.  coli  communis 
group. 

Thus  by  means  of  the  Gram  method  of  staining  one 
finds  that  the  typical  field  from  the  nursling's  stool  is 
predominantly  Gram-positive  and  consists  very  largely 
of  slender  bacilli  which  but  for  their  retention  of  the  dye 
might  be  regarded  as  colon  bacilli,  and  were  indeed  so 
regarded  by  Escherich,  who  in  his  original  studies  em- 
ployed gentian  violet  as  the  sole  staining  agent.  The 
fact  that  the  bacterial  fields  from  the  nursling  are  Gram- 
positive  is  now  familiar,  but  it  came  to  those  who  first 
observed  it  as  a  distinct  surprise.  It  was  known  that 
the  B.  coli  group  of  bacteria  are  Gram-negative,  and  as 


40        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

it  was  naturally  assumed  that  the  main  bacteria  of  the 
large  intestine  of  the  nursling  must  be  organisms  of  this 
group  (as  in  the  case  of  bottle-fed  children),  the  failure 
of  the  nursling's  fields  to  conform  to  this  assumption  at 
once  threw  doubt  on  the  view  that  the  nursling's  domi- 
nant fsecal  bacteria  are  really  colon  bacilli.  The  view 
was  put  forward  that  the  Gram-positive  character  of 
the  fields  is  due  to  the  influence  of  the  large  fat  content 
of  the  mother's  milk,1  but  this  had  soon  to  be  abandoned. 
It  was  only  through  the  use  of  suitable  cultural  methods 
that  the  mystery  was  solved. 

If  one  inoculates  agar,  gelatin,  or  bouillon  media  with 
the  mixed  flora  got  from  a  healthy  nursling  and  cultivates 
the  microorganism  in  the  presence  of  air,  bacteria  of  the 
B.  coli  type  show  themselves  regularly  to  be  the  dominant 
forms,  although  they  may  be  associated  with  diplococci, 
and  sufficiently  refined  methods  give  evidence  of  the 
presence  of  the  closely  allied  B.  lactis  aerogenes.  If, 
however,  one  grows  the  mixed  flora  on  a  suitably  pre- 
pared acid  medium,2  it  becomes  easy  to  restrict  or  even 
quite  check  the  growth  of  the  members  of  the  B.  coli 
group  and  to  demonstrate  the  presence  of  a  type  of 
microorganisms  which  grows  readily  in  this  acid  medium, 
has  a  morphology  like  that  of  the  slender  bacillary  colon 
forms,  coagulates  cow's  milk  but  does  not  act  on  human 
milk,  and  is  definitely  Gram-positive.  This  micro- 
organism, or  rather  group  of  microorganisms,  accounts 

1  Alex.  Schmidt,  "Zur  Kenntniss  der  Bakterien  der  Sauglings- 
faeces,"  Wien.  klin.  Wochenschr.,  v,  p.  643,  1892. 

2  Acid  beerwort  or  acetic-acid  bouillon,  as  suggested  by  Moro. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT         41 

for  a  small  number  of  the  Gram-positive  bacilli  seen 
in  the  microscopical  field.  Moro,  who  first  described 
these  bacteria  under  the  title  of  B.  acidophilus,  supposed 
that  their  presence  explained  fully  the  normal  Gram- 
positive  bacillary  field,  but  this  proved  to  be  an  error. 

On  subjecting  the  mixed  bacterial  flora  to  strict 
anaerobic  conditions,  Tissier  found  he  could  regularly 
cultivate  from  the  nursling's  faeces  certain  slender,  Gram- 
positive  bacilli  of  moderate  length  and  thickness  which 
not  infrequently  presented  a  bifurcated  extremity  and 
to  which  he  accordingly  gave  the  name  B.  bifidus. 
There  can  be  no  doubt  that  a  large  majority  of  the 
bacteria  seen  in  the  microscopical  fields  may  be  classed 
as  B.  bifidus.  The  bacteria  belonging  to  the  B.  bifidus 
group  possess  a  varied  morphology  which  it  seems 
desirable  to  notice  here  in  view  of  the  physiological 
importance  of  these  bacteria  during  infancy.  The  ap- 
pearance of  the  organisms  is  somewhat  different  accord- 
ing as  we  meet  with  them  in  the  faeces  or  in  culture 
media.  In  the  microscopical  fields  they  are  recognizable 
under  three  chief  forms:  (1)  a  plain  bacillary  form,1 

1  The  individuals  of  this  class  are  rods  of  varying  dimensions 
(length  3-5 /A  ;  breadth,  0.2-0.4;*).  They  are  usually  straight 
or  slightly  bent  with  somewhat  pointed  or  rounded  ends.  Oc- 
casionally, owing  to  attenuation  of  one  end  and  excessive  develop- 
ment of  the  other,  they  assume  a  comma  form.  There  is  nothing 
characteristic  about  the  arrangement  of  the  bacilli  in  smears. 
Although  distinctly  Gram-positive,  they  vary  much  in  the  degree 
in  which  they  retain  the  dye,  both  in  material  from  the  same  in- 
fant at  different  times,  and  in  different  individuals.  The  entire 
bacterium  is  frequently  not  stained  with  even  intensity,  some  parts 
of  the  organism  retaining  the  color  well,  while  other  portions  give 
it  up.  The  result  is  the  appearance  which  Escherich  expressed 


42         INFECTIONS  OF  THE  DIGESTIVE  TRACT 

(2)  a  bifid  form,  and  (3)  a  cephalated  (knobbed)  or 
headlet  form.  The  simple  form  is  by  far  the  commonest, 

in  the  course  of  his  studies  in  the  name  "punctate "  bacilli.  These 
unevenly  colored  bacteria  are  commonly  stained  in  their  middle 
portion,  while  their  ends  are  colorless,  and  this  condition  arises 
presumably  on  account  of  a  central  concentration  of  the  proto- 
plasm, which  leaves  relatively  empty  adjoining  spaces.  There 
are,  however,  other  variations  in  the  distribution  of  the  colored 
protoplasm  within  the  bacillus,  which  it  is  unnecessary  to  describe 
here.  Frequently  it  will  be  noted  that  several  bacilli  are  joined 
end  to  end,  forming  one  long,  unevenly  stained  structure.  As 
the  decolorized  portion  of  the  simple  form  of  B.  bifidus  is  still 
able  to  take  up  the  counter-stain  (e.g.  carbol  f uchsin)  with  avidity, 
we  get  apparently  Gram-negative  bacilli  in  those  cases  where  the 
protoplasm  has  been  rarefied  throughout. 

In  addition  to  the  simple  forms  of  bifidus,  a  careful  examination 
of  the  smear  will  sometimes  reveal  the  presence  of  the  bifid  form 
from  which  the  group  takes  its  name.  Sometimes  the  bifid  form 
is  very  scanty  or  absent;  at  times  it  is  moderately  abundant; 
but  it  is  never  in  health  the  dominant  form.  As  pointed  out  by 
Moro,  the  bifurcation  is  peculiar  in  these  bacteria  in  being  a  true 
division  of  the  end  or  ends  of  the  organism  rather  than  a  lateral 
branching,  such  as  one  sees  in  certain  actinomyces.  It  is  not 
necessary  to  describe  here  the  numerous  variations  in  morphology 
exhibited  by  these  bifid  bacteria.  (For  fuller  details  see  Moro, 
"  Morphologische  und  biologische  Untersunchungen  tiber  die 
Darmbakterien  des  Sauglings,"  Jahrb.  /.  Kinderheilk.,  Ixi,  p.  687, 
and  p.  870, 1905;  also  Tissier,  loc.  cit.  and  Ann.  de  VInst.  Pasteur, 
xix,  p.  109,  1905;  and  Rodella,  "  Repartition  des  Microbes  dans 
Tlntestin  du  Nourrison,"  Ann.  de  VInst.  Pasteur,  xix,  p.  404, 1905.) 

A  third  form  of  bacterium,  which  apparently  belongs  in  the 
same  group  with  the  simple  and  bifid  forms  just  described,  is 
characterized  by  a  small  enlargement  at  one  or  both  ends  —  the 
headlet  or  "Kopfchen"  form.  These  headlet  bacteria  are  seldom 
numerous  in  the  faeces  of  normal  nurslings,  and  it  is  usually 
necessary  to  look  carefully  over  the  field  to  find  them,  although 
they  are  seldom  quite  absent.  The  bodies  of  these  bacteria  are  so 
like  the  bodies  of  the  simple  form  in  their  morphology  that  one  is 
tempted  to  regard  them  as  simply  slightly  modified  examples  of 
this  simple  form  —  a  view  which  is  borne  out  by  the  results  of 


INFECTIONS  OF  THE  DIGESTIVE  TRACT         43 

and  in  many  preparations  is  the  exclusive  representative 
of  the  bifidus  type. 

cultural  studies.  Indeed,  the  microscopical  picture  itself  shows 
transitional  forms  —  bacilli  with  slight  indications  of  the  accumu- 
lation of  protoplasm  at  one  end  and  headlet  forms  which  are 
bifid  —  which  look  like  the  simple  and  the  headlet  forms.  Dumb- 
bell forms  are  at  times  seen  in  which  a  headlet  has  developed  at 
either  end  of  a  bacillus.  In  preparations  which  have  been  fixed 
by  heat  and  treated  with  Lugol's  solution  it  is  possible  to  demon- 
strate the  presence  of  granules  in  the  bodies  of  the  bacteria  of  the 
bifidus  group,  located  at  the  peripheral  ends  of  the  organism  and 
generally  limited  to  this  position.  In  hanging  drops  made  from 
fresh  material  one  finds  that  many  of  the  rod-shaped  bacteria 
possess  a  sluggish  motility  which  is  soon  lost. 

Certain  relationships  between  the  polymorphous  Gram-positive 
bacteria  which  dominate  the  microscopical  fields  (prepared  from 
the  nursling's  faecal  bacteria)  can  be  made  out  by  means  of  anaero- 
bic cultures  upon  suitable  media,  such  as  agar  or  sugar-agar, 
containing  acid.  Pure  cultures  of  the  bifidus  bacteria  are  not, 
however,  always  quite  easy  to  obtain,  as  the  B.  coli  group,  and 
some  diplococci,  which  are  facultative  anaerobes  and  grow  well  on 
the  media  just  mentioned,  are  apt  to  restrict  the  growth  of  the 
less  hardy  bifidus.  The  development  of  colonies  on  sugar-agar  is 
slow,  for  the  tiny  white  lens-shaped  smooth-edged  growths  first 
appear  in  the  deeper  parts  of  the  sugar-agar  after  about  three 
days.  (Colonies  like  these  in  all  respects  except  in  having  a  toothed 
border  are  sometimes  seen,  and  consist  of  mixtures  of  B.  bifidus 
with  B.  acidophilus.  On  further  inoculation  from  such  colonies 
there  grows,  according  to  Kahn,  only  B.  acidophilus.) 

On  microscopical  examination  of  these  colonies,  it  is  apparent 
that  we  have  to  deal  with  differently  shaped  bacteria  in  different 
colonies  and  that  even  in  the  same  colonies  there  is  a  tendency 
to  polymorphism.  Sometimes  the  bacilli  (always  Gram-positive) 
correspond  closely  to  the  simple  form  already  described,  both  in 
their  form  and  in  the  variations  in  their  staining  peculiarities. 
Some  colonies  are  made  up  of  bacteria  very  much  larger  than 
those  of  the  simple  form,  and  frequently  knobbed  or  bifurcated  or 
both.  There  seems  to  be  little  doubt  that  we  are  dealing  here 
with  various  forms  of  B.  bifidus,  and  the  frequent  development  of 
bifid  and  headlet  bacteria  of  varied  morphology  on  the  agar  medium 


44        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

The  B.  putrificus  of  Bienstock  can  sometimes  be  ob- 
tained from  the  nursling's  intestine  by  employing  a 

which  has  been  inoculated  from  the  simple  form  of  bifidus  con- 
stitutes the  best  evidence  of  close  relationship  of  these  varieties. 
In  lactose-bouillon  fermentation  tubes  which  have  been  inoculated 
from  the  faeces  of  nurslings  one  finds  in  the  sediment  large  numbers 
of  the  bifid  form  of  B.  bifidus,  after  incubation  for  twenty-four  hours. 

In  anaerobic  sugar-agar  plates  made  from  the  faeces  of  a 
human  nursling,  one  finds  colonies  which  develop  before  those 
made  up  of  the  bifidus  type,  especially  colonies  of  Staphylo coccus 
pyogenes  albus  (which  sometimes  grow  luxuriantly  on  the  surface), 
and  at  times  one  finds  varieties  of  streptococci.  An  opaque, 
white,  rumpled  layer  may  be  seen  on  aerobic  plates  made  from 
the  first  dilutions  of  the  faecal  material,  which  shows  itself,  under 
the  microscope,  to  be  made  up  of  bacilli  possessing  motility  which 
on  further  study  prove  to  be  the  common  potato  bacilli  (B.  mesen- 
tericus  vulgatus,  Fliigge). 

In  the  study  of  the  bacterial  flora  of  the  intestinal  tract  (es- 
pecially in  its  lowest  portions,  colon,  sigmoid,  and  rectum)  the 
routine  employment  of  pasteurization  at  80°  C.  for  fifteen  or  twenty 
minutes  previous  to  making  aerobic  and  anaerobic  plates,  is  of 
much  value.  Most  vegetative  forms  of  bacteria  present  in  the 
human  intestine  are  killed  by  this  exposure  to  heat,  and  only 
those  races  survive  which  can  form  spores  and  have  done  so. 
The  application  of  this  procedure  is  important  both  in  the  study 
of  physiological  conditions  and  for  the  detection  of  pathological 
peculiarities  of  the  intestinal  flora.  On  employing  this  method 
in  the  study  of  the  intestinal  flora  of  nurslings,  it  is  found  that  by 
the  use  of  suitable  culture  media,  several  forms  of  spore-bearing 
bacteria  are  present  as  regular  or  almost  regular  inhabitants  of 
the  lower  intestine. 

Among  the  microorganisms  which  are  brought  to  notice  by 
these  methods  is  a  variety  which  makes  on  agar  small,  cottony 
colonies,  of  somewhat  indefinite  outline,  giving  rise  to  small  gas- 
production  which  may  cause  slight  rents  in  the  medium.  These 
colonies  consist  of  Gram-positive  bacilli,  often  colored  only  in  places 
by  the  dyestuff,  which  sometimes  carry  a  knob  at  one  end,  which 
can,  in  certain  instances,  be  shown  to  be  spores.  These  spore-bear- 
ing bacilli  are  to  be  regarded  as  identical  with  the  headlet  bacteria 
already  mentioned,  and  are  thus  the  representatives  of  the  resistant 


INFECTIONS  OF  THE  DIGESTIVE  TRACT         45 

medium  of  sterilized  egg-white,  but  its  presence  in  more 
than  small  numbers  is  exceptional  and  it  may  be  entirely 
absent. 

A  more  important  anaerobic  spore-bearing  micro- 
organism than  B.  putrificus  is  B.  aerogenes  capsulatus* 
which  can  be  demonstrated  by  its  growth  on  sterilized 
milk  to  which  an  abundance  of  faecal  bacteria  has 
been  added  or  by  its  ready  growth  on  blood-agar  with 
or  without  the  addition  of  sugar.  So  long  ago  as  1894 
Fliigge  found  that  the  faeces  of  children  nourished  wholly 
on  mother's  milk  contained  Botkin's  Bacillus  butyricus, 
and  we  now  know  from  the  critique  of  Grassberger  and 
Schottenfroh  that  Botkin's  bacillus  in  reality  represents 
two  distinct  microorganisms,  each  of  which  is  capable 

or  spore-forming  variety  of  B.  bifidus.  The  headlet  bacteria  have 
a  morphological  resemblance  to  another  spore-forming  anaerobe, 
B.  putrificus,  which  by  appropriate  methods  of  culture  can  some- 
times be  isolated  from  the  nursling's  stool.  The  resemblance  is 
so  close  that  in  faecal  smears  submitted  to  microscopical  examina- 
tion it  is  hardly  possible  to  make  a  distinction  with  confidence. 

1  This  organism  is  known  by  different  names  in  different  coun- 
tries. The  name  B.  aerogenes  capsulatus  was  given  to  it  by  Pro- 
fessor Welch  and  is  the  name  by  which  it  is  best  known  in  the 
United  States.  The  organism  is  identical  with  the  gas-phlegmon 
bacillus  of  Fraenkel  and  probably  with  the  granulo-bacillus  im- 
mobilis  liquefadens  of  Grassberger  and  Schottenfroh.  In  France 
the  organism  is  known  as  B.  perfringens  (Veillon  and  Zuber). 
In  England  Klein  described  an  organism  which  he  called  B.  en- 
teritidis  sporogenes,b\it  it  is  doubtful  if  he  was  dealing  with  pure 
cultures,  although  it  appears  probable  that  he  had  B.  aerogenes 
capsulatus  in  his  cultures.  A  trinomial  name  is  considered  objec- 
tionable by  botanists,  and  hence  Migula  proposed  the  name  B. 
Welchii  for  B.  aerogenes  capsulatus,  but  the  latter  name  is  now  so 
firmly  established  in  the  United  States  that  it  is  doubtful  if  it 
will  be  displaced.  Welch's  bacillus  is  often  spoken  of  as  "the 
gas-bacillus." 


46         INFECTIONS  OF  THE  DIGESTIVE  TRACT 

of  inducing  decomposition  with  the  production  of 
butyric  acid.  Of  these  the  granulo-baciUus  immobilis 
liquefaciens  is  probably  identical  with  B.  aerogenes 
capsulatus  (but  not  pathogenic),  and  was  described  by 
Passini  in  1902  as  occurring  in  the  faeces  of  normal  nurs- 
lings. This  is  undoubtedly  true,  but  I  wish  to  empha- 
size the  fact  that  the  organism  normally  occurs  under 
these  conditions  in  only  very  small  numbers  as  com- 
pared with  bacteria  of  the  bifidus  type.  One  may  look 
through  many  Gram-stained  fa3cal  fields  without  find- 
ing any  evidence  of  its  presence.  The  physiological 
significance  of  this  fact  will  later  be  pointed  out.  The 
other  organism  which  appears  to  have  been  included 
in  Botkin's  description  of  his  B.  butyricus,  is  one  closely 
related  to  B.  aerogenes  capsulatus  in  morphology.  It  is, 
however,  motile,  does  not  liquefy  gelatin,  and  readily 
forms  spores  —  features  which  distinguish  it  sufficiently 
for  the  present  enumeration  *  of  the  anaerobic  flora. 
This  organism  has  been  found  in  the  faeces  of  nurslings, 
but  is  of  much  less  importance  than  B.  aerogenes  capsu- 
latus. Occasionally,  too,  the  nursling's  fa3ces  have  been 
found  to  contain  the  bacillus  of  malignant  oedema 
(Passini)  and  a  very  closely  related  microorganism  which 
differs  from  the  bacillus  of  malignant  cedema  in  being 
Gram-positive  and  in  making  skatol. 

One  may  summarize  the  results  of  cultural  studies  of 
the  bacterial  flora  of  normal  human  nurslings  as  follows. 
The  stools  and  the  contents  of  the  large  intestine  from 

1  It  is  known  as  the  granulo-bacillus  mobilis  nons-liquefadens 
of  Grassberger  and  Schottenfroh. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT         47 

these  infants  number  among  their  inhabitants  the 
following:  B.  bifidus  communis  and  the  headlet  bac- 
teria (which  are  probably  varieties  of  B.  bifidus),  B.  coli 
communis,  and  B.  lactis  aerogenes,  B.  acidophilus,  B. 
aerogenes  capsulatus,  and  certain  intestinal  streptococci.1 
It  should  be  noted  that  of  these  bacteria  the  dominant 
form,  B.  bifidus  (and  in  the  upper  part  of  the  large  intes- 
tine, B.  coli  communis  and  B.  lactis  aerogenes),  is  one 
which  forms  lactic  acid  on  sugar  media,  is  antiputrefac- 
tive,  and  does  not  attack  proteids.  It  should  also  be 
observed  that  B.  aerogenes  capsulatus,  the  most  impor- 
tant representative  of  the  putrefactive  type  of  in- 
testinal bacteria,  is  an  extremely  scarce  organism,  and 
finally,  that  spore-holding  bacteria  and  free  spores  are 
of  rare  occurrence  (relatively)  in  the  faeces  and  contents 
of  the  large  intestine. 

What  has  been  already  said  regarding  the  results  of 
microscopical  and  cultural  investigation  of  the  nursling's 
faeces  makes  it  clear  that  the  picture  which  we  get  from 
the  former  method  is  quite  different  from  that  furnished 
by  the  latter.  Whereas  one  would  conclude  from  the 
microscopical  field  that  he  was  dealing  chiefly  with  one 
race  of  bacteria  (B.  bifidus)  supplemented  by  very  few 
other  forms,  cultural  methods  which  include  anaerobic 

1  Less  constant  inhabitants  are  the  following,  Staphylococcus 
pyogenes  albus,  intestinal  diplococci,  B.  putrificus,  the  motile 
butyric  acid  bacillus  (Amylobacteria  of  Briiber  or  granulo-badllus 
mobilis  non-liquefadens  of  Grassberger  and  Schottenf roh) ;  B. 
mesentericus  vulgatus  (Fliigge) ;  certain  actinomyces,  especially 
Actinomyces  chromogenes;  sarcinse  ;  Oidium  albicans,  and  various 
yeasts. 


48         INFECTIONS  OF  THE  DIGESTIVE  TRACT 

studies  on  suitable  media  show  that  the  flora  is  in 
reality  more  varied  and  that  forms  physiologically  im- 
portant are  present  of  which  one  obtains  no  suggestion 
from  the  fields  alone.  Such  a  picture,  taken  by  itself, 
is  misleading  in  certain  respects,  but  representative  in 
others.  The  microscopic  fields  of  the  faeces  showing 
mainly  one  form  represent  with  a  fair  degree  of  accuracy 
the  bacterial  conditions  in  the  faeces,  for  here  the  other 
types  are  in  reality  very  feebly  represented.  The  cul- 
tural methods  which  it  is  almost  impossible  to  employ 
in  such  a  way  as  to  make  them  give  an  accurate  insight 
into  the  actual  quantitative  relations  of  the  bacteria 
present,  might  easily  mislead  one  into  supposing  that 
the  subsidiary  varieties  thus  brought  to  light  are  more 
abundant  in  the  faeces  than  is  actually  the  case.  But 
if  we  look  at  these  cultural  results  as  indications,  not  of 
the  quantitative  relations  of  the  faecal  flora,  but  rather 
as  indices  of  the  conditions  prevailing  at  higher  levels 
of  the  large  intestine,  where  one  type  is  no  longer  so 
dominant,  these  results  become  instructive  instead  of 
confusing. 

Distribution  of  the  Bacterial  Flora  in  the  Digestive 
Tract  of  the  Nursling.  —  Although  the  distribution  of  the 
bacteria  of  the  digestive  tract  in  normal  or  approximately 
normal  nurslings  has  not  yet  received  much  attention, 
it  is  a  subject  which  cannot  be  ignored,  for  it  is  capable 
of  giving  us  information  in  regard  to  the  nature  of  the 
decompositions  that  are  possible  at  different  levels  of 
the  tract  in  health,  these  decompositions  being  often  of 
a  different  nature  in  disease  from  those  which  occur  in 


INFECTIONS  OF  THE  DIGESTIVE  TRACT         49 

health.  Escherich,  one  of  the  few  students  of  this  sub- 
ject, found  that  the  number  of  intestinal  bacteria  in- 
creases gradually  from  above  downward  in  the  small 
intestine,  undergoing  a  sudden  and  extreme  increase  at 
the  level  of  the  caecum.  Even  as  high  as  the  duodenal 
level  moderate  numbers  of  microorganisms  could  be 
found  corresponding  to  the  types  of  the  B.  coli  and  B. 
lactis  aerogenes  groups.  Schmidt,  making  use  of  Weigert's 
method  for  staining  fibrin,  noticed  that  a  preponderance 
of  Gram-positive  over  Gram-negative  forms  does  not 
begin  until  the  level  of  the  colon  is  reached.  From  the 
middle  of  the  colon  downward,  the  characteristic  Gram- 
positive  fa3cal  flora  begins  to  dominate  the  picture  and 
appears  exclusively  present  in  the  rectum  —  a  striking 
evidence  of  the  fundamental  difference  between  the  flora 
of  the  upper  and  lower  portions  of  the  intestine. 

I  have  had  an  opportunity  to  make  microscopical 
examinations  (using  Gram's  method  of  staining)  of  the 
contents  of  the  digestive  tract  of  nursling  infants  dying 
within  the  first  six  months  from  conditions  not  closely 
connected  with  the  digestive  tract  (e.g.  acute  broncho- 
pneumonia).  On  comparing  the  results  of  these  exami- 
nations with  those  obtained  by  Moro  by  the  use  of  the 
Escherich-Weigert  fibrin  stain,  they  were  found  to  be  so 
nearly  alike  in  their  leading  features  as  to  make  it 
probable  that  the  following  description,  based  on  these 
two  sets  of  observations,  is  generally  applicable  to  the 
case  of  healthy  nursling  children. 

In  normal  nurslings  the  mouth  contains  few  bacteria, 
and  such  as  it  contains  are  for  the  most  part  organisms 


50         INFECTIONS  OF  THE  DIGESTIVE  TRACT 

derived  from  the  skin  and  nipple  —  Staphylococcus 
pyogenes  aureus,  bacilli  of  the  B.  coli  group  and  B.  lactis 
aerogenes.  In  the  stomach  the  number  of  bacteria  is 
also  small,  and  the  bacterioscopic  picture  shows  usually 
a  few  positive  or  negative  diplococci  or  streptococci  or 
negative  cocco-bacilli  or  positive  or  negative  bacilli, 
suggesting  the  B.  coli  and  B.  lactis  aerogenes  group.  The 
duodenum  and  jejunum  generally  contain  remarkably 
few  microorganisms,  owing  mainly  to  the  rapidity  with 
which  the  food  passes  through  this  region.  When  food 
in  the  jejunum  is  present  in  larger  amount  than  is  usual, 
the  numbers  of  bacteria  are  correspondingly  increased, 
but  it  is  the  rule  that  the  greater  part  of  the  small  intes- 
tine is  almost  free  from  bacteria  and  that  they  do  not 
become  really  numerous  until  the  level  of  the  lower  ileum 
is  reached.  Here  there  is  almost  regularly  an  abrupt 
increase  in  the  bacterial  flora.  In  the  csecum  (and  like- 
wise in  the  vermiform  appendix)  the  bacterial  increase 
is  enormous.  The  normal  bacteria  of  the  greater  por- 
tion of  the  small  intestine  are  Gram-negative,  short  bacilli 
of  the  coli  and  lactis  aerogenes  variety,  mixed  sometimes 
with  a  few  positive  and  negative  coccal  forms.  In  the 
lower  ileum  the  Gram-negative  forms  become  mixed  with 
those  of  the  bifidus  type,  especially  the  punctate  bacilli. 
The  transition  from  lower  ileum  to  caecum  marks,  as  a 
rule,  a  striking  change  in  the  proportions  of  coli  and 
bifidus  types,  since  the  former  lose  their  dominant  nu- 
merical position.  This  ascendency  of  the  bifidus  type  is 
so  great  in  the  transverse  and  descending  colon  that  all 
other  bacteria  in  these  regions  are  numerically  incon- 


INFECTIONS  OF  THE  DIGESTIVE  TRACT        51 

spicuous  and,  as  in  the  rectum,  this  type  has  the  ap- 
pearance of  being  present  in  pure  culture. 

The  bacterial  flora  of  the  intestinal  tract  of  the  nurs- 
ling is  thus  only  moderately  numerous  as  regards  variety. 
The  bacteria  are  concentrated  in  the  regions  that  lie 
between  the  lower  ileum  and  the  anus,  the  ileocsecal 
region  presenting  more  kinds  of  bacteria  than  the  lower 
colon  and  more  organisms  capable  of  being  cultivated. 
The  comparatively  small  numbers  of  bacteria  found  in 
the  small  intestine  has  its  explanation  partly  in  the 
small  amount  of  food  that  lodges  there,  partly  perhaps 
in  the  bacteriolytic  action  of  the  succus  entericus. 
Wherever  particles  of  transformed  casein  are  found,  there 
also  will  be  found  bacteria  in  abundance,  but  with  the 
exception  of  the  lower  ileum  the  small  intestine  does  not 
harbor  food  masses  to  any  considerable  extent.  The 
bacteriolytic  action  of  the  succus  entericus  is  moderate 
but  appreciable.  The  epithelial  cells  are  said  to  contain 
an  antitryptic  ferment,  and  this  passes  to  some  extent 
into  the  succus  entericus,  where  it  is  perhaps  capable 
of  exerting  a  restraining  influence  on  that  peptonization 
of  proteids  which  is  the  first  essential  step  toward  putre- 
factive decomposition. 

Various  attempts  have  been  made  to  form  a  numerical 
estimate  of  the  numbers  of  living  and  dead  bacteria 
present  at  different  levels  of  the  colon  and  to  deter- 
mine what  proportion  of  bacteria  have  been  rendered 
lifeless  during  their  descent  through  the  colon.  Eberle, 
who  compared  the  numbers  of  bacteria  seen  in  micro- 
scopical preparations  with  the  results  of  plate  cultures, 


52         INFECTIONS  OF  THE  DIGESTIVE  TRACT 

concluded  that  from  four  and  five-tenths  to  ten  per  cent, 
of  the  faecal  bacteria  are  capable  of  growing  on  the 
common  culture  media.  Klein  got  only  about  one  per 
cent,  to  grow;  Schmidt  and  Strasberger,  basing  their 
estimates  on  a  different  method  of  procedure,  which  in- 
volved weighing  masses  of  bacteria  in  order  to  avoid  the 
errors  incidental  to  counting,  came  to  the  conclusion  that 
only  about  0.07  per  cent,  of  the  bacteria  are  viable.  It 
is,  however,  easy  to  see  that  none  of  these  methods  can 
claim  to  give  even  approximately  correct  results,  because 
we  have  in  the  nursling's  faeces  many  anaerobic  bacteria 
which  grow  only  under  special  conditions,  and  acidophile 
bacteria  which  require  special  media  for  their  cultiva- 
tion, and  these  special  conditions  have  not  yet  been 
furnished  by  those  who  have  made  numerical  estimates. 
Moreover,  it  is  extremely  probable  that  on  their 
way  through  the  large  intestine  many  bacteria  undergo 
autolysis  and  wholly  disappear.  Hence  the  problem 
of  determining  the  fate  of  the  bacteria  in  their  descent 
through  the  nursling's  colon  is  one  beset  with  diffi- 
culties so  considerable  as  to  make  numerical  com- 
parisons an  unpromising  field  for  study.  There  can, 
however,  be  no  doubt  that,  as  already  stated,  the  living 
bacteria  of  the  intestine  usually  undergo  a  marked 
diminution  in  numbers  on  their  passage  through  the  colon 
and  that  a  large  proportion  of  them  seen  under  the 
microscope  in  preparations  from  the  faeces  are  not  viable, 
even  on  anaerobic  plates.  The  histological  signs  of  dis- 
integration are  often  visible.  Among  the  causes  of  the 
death  of  intestinal  bacteria,  under  normal  conditions, 


INFECTIONS  OF  THE  DIGESTIVE  TRACT         53 

the  diminution  of  food  and  the  lack  of  moisture  prob- 
ably are  among  the  most  effective. 

A  satisfactory  study  of  the  products  of  the  mixed  fsecal 
flora  from  normal  nurslings  has  not  yet  been  made.  One 
fact  nevertheless  stands  out,  namely,  that  on  sugar 
bouillon  containing  blood  the  volatile  acid  or  acids  pro- 
duced give  a  molecular  weight  corresponding  closely  to 
that  for  acetic  acid.  The  presence  of  only  insignificant 
amounts  of  higher  volatile  fatty  acids  points  to  the 
absence  of  considerable  numbers  of  anaerobic  putrefac- 
tive bacteria,  since  these  form  the  higher  acids,  pro- 
vided anaerobic  conditions  be  secured. 

In  harmony  with  this  is  our  observation  that  ten  or 
twenty  cubic  centimeters  of  a  ten  per  cent,  suspension 
of  fsecal  bacteria  from  a  normal  nursling  may  be  in- 
jected into  a  rabbit,  which  is  then  incubated,  without 
inducing  a  gas-liver  from  putrefactive  anaerobes  (B. 
aerogenes  capsulatus). 

The  mixed  fsecal  flora  when  grown  on  plain  bouillon 
makes  indol,  doubtless  owing  to  the  multiplication  of 
colon  bacilli. 

The  Infection  of  the  Nursling's  Digestive  Tract  and  the 
Relation  of  the  Microorganisms  to  the  Permanent  Bac- 
terial Flora.  —  One  naturally  asks  the  question :  What  is 
the  origin  of  the  normal  intestinal  flora  of  the  nursling 
child?  How  does  it  happen  that  the  meconium,  which 
is  a  sterile  medium  derived  from  the  intestinal  juices 
and  epithelial  cells,  becomes  the  seat  of  bacterial  life? 
As  the  mother's  milk  is  normally  free  from  bacteria 
when  it  issues  from  the  breast,  one  cannot  attribute  the 


54         INFECTIONS  OF  THE  DIGESTIVE  TRACT 

first  infection  of  the  digestive  tract  to  necessary  bacterial 
inhabitants  of  the  milk.  But  since  a  portion  of  the 
milk  may  come  in  contact  with  the  nipple,  and  the  child's 
lips  come  into  contact  with  the  skin  of  the  breast  as  well 
as  the  surface  of  the  nipple,  it  is  clear  that  any  bacteria 
living  on  or  near  the  nipple  may  find  their  way  into  the 
digestive  tract  of  the  child.  It  might  be  supposed  that 
the  gastric  juice  or  the  enterokinase  of  the  small  intes- 
tine would  form  an  obstacle  to  the  passage  of  living  bac- 
teria into  the  intestine,  but  it  has  been  well  demonstrated 
that  these  defenses  even  in  the  fully  developed  form  in 
which  they  exist  in  adults,  are  only  partial,  and  that  many 
living  bacteria  readily  pass  from  the  stomach  into  the 
small  intestine  in  newly  born  children.  In  the  case  of 
very  young  children,  the  secretion  of  a  bactericidal  gastric 
juice  is  probably  but  a  feeble  protection  against  the  pas- 
sage of  living  bacteria  into  the  intestine,  and  even  were 
it  in  part  effective,  there  might  frequently  be  oppor- 
tunity for  bacteria,  located  in  the  interior  of  curds,  to 
pass  from  the  stomach  into  the  intestine.  Moreover, 
if  the  bacteria  were  present  in  large  numbers  in  the  stom- 
ach, some  of  them  would  almost  certainly  pass  into  the 
intestinal  tract,  although,  as  has  already  been  seen  in 
discussing  the  distribution  of  the  bacteria  of  the  intes- 
tinal tract,  it  is  usual  to  observe  a  considerable  falling 
off  in  the  numbers  of  microorganisms  as  one  passes  from 
the  stomach  to  the  duodenum  and  jejunum.  It  seems 
probable,  then,  on  the  grounds  already  stated,  that  an 
infection  of  the  intestine  by  bacteria  occurs  through  the 
mouth.  This  probability  was  rendered  a  certainty  by 


INFECTIONS  OF  THE  DIGESTIVE  TRACT         55 

the  observations  of  Escherich  on  a  case  of  atresia  ani 
in  which  he  was  able  to  find  in  the  intestine  the  obligate 
milk  stool  bacteria,  B.  coli  and  B.  lactis.  Moro,  fur- 
thermore, found  B.  acidophilus  in  human  milk  and  on 
the  areola  in  nursing  women  and  drew  the  inference  that 
this  organism  reaches  the  intestine  by  way  of  the  mouth. 
The  passage  of  this  particular  organism  which  is  so 
resistant  in  acid  media  is,  of  course,  not  surprising. 
Other  observations  were  made  by  Moro  upon  human 
milk  in  the  hope  of  finding  there  B.  bifidus  communis  and 
of  thus  explaining  the  presence  of  this  microorganism  or 
group  of  bacteria  in  the  intestine  of  nursling  children; 
but  although  he  made  numerous  anaerobic  sugar-agar 
cultures  from  various  samples  of  human  milk  (where  no 
precautions  had  been  taken  to  cleanse  the  nipple),  he 
was  unable  to  obtain  anything  except  negative  results, 
although  relatively  large  quantities  of  milk  were  regu- 
larly used  in  making  the  cultures.  Moro  was  indeed 
unable  to  cultivate  any  strictly  anaerobic  bacteria  from 
human  milk.  On  the  other  hand,  he  regularly  found 
Staphlococcus  albus,  which  is  well  known  to  be  present 
on  or  near  the  epidermis;  sometimes  colon  bacilli  and 
pseudodiphtheria  bacilli ;  and  in  exceptional  cases  strep- 
tococci, sarcinse,  and  Micrococcus  candicans;  and  once 
a  fluorescent  bacillus,  but  never  anaerobes. 

A  further  observation  bearing  on  this  question  was 
made  by  Moro.  A  newly  born  child  received  only  ster- 
ilized milk  from  the  second  until  the  sixth  day.  The 
excretion  of  meconium  took  place  in  the  usual  way  and 
the  characteristic  bacterial  types  were  found  in  it. 


56         INFECTIONS  OF  THE  DIGESTIVE  TRACT 

The  first  milk  stool  appeared  on  the  fifth  day  and  con- 
tained the  physiological  flora.  It  is  evident,  therefore, 
that  the  organisms  present  in  this  case  must  have  had 
another  source.  The  possibility  of  the  presence  of 
B.  bifidus  in  the  mouth  of  the  child  was  then  excluded  by 
the  observation  that  anaerobic  organisms  do  not  grow 
from  the  mouth  secretion  of  newly  bora  children.  As 
it  thus  appeared  clear  that  the  infection  of  the  intestinal 
tract  by  bifidus  does  not  occur  by  way  of  the  mouth, 
there  remained  only  one  possibility ;  namely,  that  the 
infection  occurred  through  the  anus.  A  study  of  the 
organisms  of  the  meconium  has  made  it  appear  very 
probable  that  this  is  the  mode  of  infection  with  B. 
bifidus. 

The  bacteria  of  the  meconium  were  first  carefully  stud- 
ied by  Escherich,  who  pointed  out  that  the  originally 
sterile  meconium  very  easily  acquires  bacteria  charac- 
terized by  their  relative  sparcity  and  considerable  variety 
and  the  presence  of  certain  spore-bearing  organisms. 

Among  the  constant  flora  are  coccal  forms  in  relatively 
large  numbers;  some  short  bacilli,  including  B.  coli 
communis,  and  some  varieties  of  spore-bearers.  One 
form  of  spore-bearer  is  the  so-called  headlet  bacterium 
already  mentioned,  and  a  thicker  form  which  was  iden- 
tified by  Kohn  as  B.  subtilis.  On  gelatin  plates  the  most 
abundant  organisms  are  usually  B.  coli  communis,  which 
is  sometimes  associated  with  liquefying  streptococci.  In 
fact,  the  presence  of  liquefying  bacteria  in  the  meconium 
is  rather  characteristic  of  the  meconial  period,  and  this 
peculiarity,  under  normal  conditions,  ceases  abruptly 


INFECTIONS  OF  THE  DIGESTIVE  TRACT         57 

with  the  onset  of  the  milk-stool  period.  B.  lactis  aero- 
genes  was  not  found  in  the  meconial  stools.  It  appears 
from  Moro's  observations,  which  I  can  corroborate,  that 
bacteria  of  the  B.  coli  type  may  appear  in  agar  plates 
as  early  as  ten  hours  after  birth.  Somewhat  later, 
various  coccal  forms  may  appear ;  in  the  course  of  forty- 
eight  hours  the  bacterioscopic  fields  may  show  bacilli 
which  are  Gram-positive  and  which  in  some  instances 
show  typical  bifurcations  and  through  anaerobic  culture 
on  sugar-agar  may  prove  to  be  B.  bifidus  communis. 
Still  a  little  later,  B.  aerogenes  capsulatus  may  make  its 
appearance,  and  about  this  time,  too,  spore-bearing  cylin- 
drical bacilli  may  appear.  The  very  early  occurrence 
of  B.  bifidus  in  the  meconium  is  a  striking  fact,  since  it 
appears  hardly  possible  to  explain  its  presence  there 
so  soon  after  birth  on  the  supposition  that  bifidus  has 
entered  by  the  portal  of  the  mouth.  It  appears,  there- 
fore, upon  the  whole,  extremely  probable  that  the  infec- 
tion of  the  gut  in  newly  born  children  with  B.  bifidus 
communis  is  by  way  of  the  anus  and  that  the  air  is  the 
source  of  the  infection.  It  is  interesting  to  note  that 
even  before  the  appearance  of  B.  bifidus  in  the  meconial 
stools  the  colon  bacillus  is  represented  there.  The  pres- 
ence of  the  colon  bacillus,  like  the  presence  of  B.  bifidus, 
cannot  be  explained  at  this  early  period  by  an  invasion 
through  the  mouth,  although,  as  already  stated,  the  colon 
bacillus  may  enter  the  intestine  by  way  of  the  mouth  at 
a  later  period.  Both  these  organisms,  B.  bifidus  and  B. 
coli,  possess  motility,  and  it  is  probably  by  virtue  of  this 
motility  that  they  find  their  way  into  the  lower  intestinal 


58        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

tract,  and  into  the  meconium  on  which  they  are  able  to 
live,  although  it  is  only  a  fair  culture  medium.  The 
meconium  thus  contains  forms  which  are  the  forerunners 
of  the  permanent  intestinal  bacteria.  In  the  case  of 
B.  aerogenes  capsulatus,  it  appears  to  me  that  its  presence 
in  the  meconium  can  hardly  be  explained  on  the  ground 
of  its  possessing  motility,  since  it  is  questionable  whether 
this  organism  is  ever  at  all  motile,  and  certain  that  as  a 
rule  it  is  non-motile.  It  is  possible  that  it  may  be  found 
in  the  meconium  in  extremely  small  numbers  as  a  result 
of  contamination  at  the  time  of  the  passage  of  the  meco- 
nium, since  B.  aerogenes  capsulatus  is  so  widely  distributed 
and  so  common  an  inhabitant  of  the  air.  Possibly,  also, 
the  same  explanation  would  apply  to  the  presence  of  B. 
putrificus,  a  spore-bearing  organism  which  is  common  in 
dust. 

We  see  thus  that  while  non-motile  forms  of  organisms 
like  B.  lactis  aerogenes,  B.  acidophilus,  staphylococci,  and 
streptococci  can  find  their  way  into  the  intestinal  tract 
only  by  way  of  the  mouth,  through  the  milk  (being  un- 
endowed with  motility),  the  members  of  the  colon 
bacillus  group  may  invade  the  digestive  tract  either 
through  the  mouth  or  the  anus,  and,  finally,  that  B. 
bifidus,  the  chief  obligate  bacterium  of  the  milk-stools 
of  nurslings  and  a  regular  and  permanent  inhabitant  of 
the  meconium,  reaches  the  intestinal  tract  only  by  way 
of  the  anus.  It  is  noticeable  that  the  meconium  contains 
a  considerable  proportion  of  spore-forming  bacteria; 
that  is,  of  bacteria  capable  of  resisting  unfavorable  in- 
fluences. Whether  they  find  their  way  into  the  intes- 


INFECTIONS  OF  THE  DIGESTIVE  TRACT         59 

tine  as  spores  or  in  their  vegetative  form  is  not  clear 
and  is  probably  not  important.  They  do,  however, 
sporulate  in  the  meconium,  which  may  perhaps  be  inter- 
preted as  indicating  that  the  meconium  is  a  poor  rather 
than  a  good  nutrient  medium  for  these  organisms,  al- 
though I  do  not  feel  sure  that  this  interpretation  is 
absolutely  safe.  It  appears  that  the  meconium  is  in 
general  a  poor  medium  for  bacteria,  and  this  fact  ex- 
plains satisfactorily  its  relative  poverty  in  bacteria. 
The  poor  nutrient  character  of  the  meconium  may  be 
due  in  part  to  its  inspissation  and  in  part  to  its  relatively 
high  content  of  bile  acids,  which  would  tend  to  prevent 
the  rapid  multiplication  of  invading  organisms.  It  is 
doubtless  true  that  the  meconium,  in  consequence  of 
these  properties,  exercises  a  selective  action  on  the  in- 
vaders of  the  lower  intestine,  discouraging  all  those 
vegetative  forms  that  are  non-resistant  either  through 
the  inability  to  adapt  themselves  to  the  peculiar  con- 
ditions of  the  medium  or  through  the  inability  to  form 
spores.  The  meconium  is  therefore  to  be  regarded  as 
possessing  physiological  functions  instead  of  being  an 
indifferent  substance.  The  main  physiological  function 
of  this  meconial  plug  is  apparently  the  exclusion  of 
numerous  foreign  types  of  bacteria  and  the  encourage- 
ment of  those  organisms  which  are  destined  to  become 
the  permanent  inhabitants  of  the  nursling's  digestive 
tract. 

Bacterial  Flora  of  Bottle-fed  Children.  —  If  one  makes 
a  comparison  of  the  bacteria  of  the  digestive  tract  of 
children  fed  on  cow's  milk  with  the  flora  which  has 


60         INFECTIONS  OF  THE  DIGESTIVE  TRACT 

already  been  described  as  characteristic  of  the  digestive 
tract  in  breast-fed  children,  one  finds  many  points  of 
resemblance  but  also  some  typical  and  important  differ- 
ences. In  general  it  may  be  said  that  the  number  of 
bacterial  forms  present  in  the  digestive  tract  of  children 
nourished  with  cow's  milk  is  considerably  greater  than 
in  the  case  of  breast-fed  children.  This  is  true  even 
where  children  are  fed^on  cow's  milk  that  has  been 
sterilized  by  boiling  or  by  pasteurization.  And  the 
difference  in  number  is  even  greater  in  those  cases  where 
sterilization  has  not  been  practiced,  since  this  procedure 
destroys  a  large  proportion  of  the  bacteria  present  in 
the  milk  and  especially  the  lactic  acid  producers.  Where 
sterilized  milk  is  employed  the  increase  in  the  number  of 
bacteria  in  the  digestive  tract  as  compared  with  the 
number  of  varieties  present  in  the  intestines  of  breast- 
fed children  is  dependent  at  least  in  part  upon  the 
presence  of  anaerobic  bacteria  or  facultative  varieties 
capable  of  forming  spores. 

That  the  number  of  bacteria  should  ordinarily  be 
greater  in  children  fed  on  cow's  milk  than  in  children 
fed  on  mother's  milk  can  cause  no  surprise,  when  one 
remembers  how  abundant  are  the  microorganisms  present 
in  most  specimens  of  cow's  milk.  The  number  ordi- 
narily ranges  from  one  or  two  thousand  bacteria  per  cubic 
centimeter  *  in  cow's  milk  that  has  been  collected  with 
the  utmost  precautions  in  regard  to  cleanliness"of  pres- 
ervation, up  to  several  million  per  cubic  centimeter. 

1  Under  very  special  conditions  milk  can  be  obtained  which  has 
a  far  smaller  number  of  bacteria. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT         61 

Although  the  character  of  the  bacteria  is  much  more 
important  than  their  number,  those  specimens  of  milk 
which  contain  the  largest  numbers  are  also  most  likely 
to  contain  the  forms  which,  aside  from  the  inciters  of 
typhoid  fever  and  dysentery,  are  most  injurious;  that 
is,  especially,  the  streptococci  and  the  putrefactive  anae- 
robes. Ordinarily  good  milk  frequently  contains  from 
thirty  to  one  hundred  thousand  bacteria  per  cubic  cen- 
timeter. Thus  we  see  that  there  is  good  reason  why  the 
mouth  and  stomach  are  liable  to  contain  much  larger 
numbers  of  bacteria  in  the  case  of  children  fed  on  cow's 
milk  than  in  the  case  of  breast-fed  children,  and  it  is 
further  clear  that  the  actual  number  will  vary  somewhat 
with  the  character  of  the  milk  that  is  employed.  As  in 
the  case  of  breast-fed  children,  there  is  a  marked  dimi- 
nution in  the  number  of  bacteria  found  in  the  upper  part 
of  the  small  intestine  as  compared  with  the  bacteria  in 
the  stomach.  This  diminution,  which  probably  de- 
pends in  part  on  the  bactericidal  action  of  the  gastric 
juice  and  intestinal  juices,  tends  to  bring  about  in  the 
small  intestine  a  greater  equality  in  the  number  of  bac- 
teria in  breast-fed  and  bottle-fed  children  than  is  ob- 
served at  higher  levels.  Nevertheless,  even  in  the  lower 
part  of  the  small  intestine  and  throughout  the  large 
intestine,  the  number  of  bacterial  species  appears  to  be 
as  a  rule  greater  in  the  case  of  children  fed  on  cow's  milk 
than  in  the  case  of  nurslings. 

Many  of  the  bacterial  forms  which  have  already  been 
described  as  regular  inhabitants  of  the  nursling's  intes- 
tinal tract  are  also  inhabitants  of  the  digestive  tract  of 


62         INFECTIONS  OF  THE  DIGESTIVE  TRACT 

bottle-fed  children.  We  find  especially  that  this  resem- 
blance holds  true  with  regard  to  the  B.  lactis  aerogenes 
group,  the  B.  coli  group,  the  B.  acidophilus  group,  and 
the  group  of  organisms  which  we  have  come  to  know  as 
B.  bifidus.  As  regards  B.  bifidus,  however,  we  find  that 
there  is  a  striking  difference  between  the  nursling  and  the 
bottle-fed  child.  In  nurslings  the  B.  bifidus  is  the  domi- 
nant type  throughout  the  greater  part  of  the  large  intes- 
tine; in  the  bottle-fed  child  the  group  of  B.  bifidus  is 
fairly  well  represented,  as  a  rule,  throughout  the  large 
intestine  and  also  in  the  lower  part  of  the  small  intestine, 
but  it  is  by  no  means  the  dominant  organism.  The  place 
of  preponderance  is,  in  this  case,  occupied  by  organisms 
of  the  B.  coli  type,  and  we  thus  find  that  the  microscopi- 
cal picture  in  the  case  of  the  bottle-fed  child  shows  us  a 
field  in  which  a  majority  of  the  microorganisms  present 
are  Gram-negative  instead  of  Gram-positive,  as  is  the 
case  in  nurslings.  In  addition  to  these  leading  types 
of  organisms  in  the  case  of  bottle-fed  children  we  have  to 
include  certain  positive  and  negative  diplococci,  some 
of  which  are  seen  in  chains  while  others  appear  as  di- 
plococci only.  An  organism  described  by  Kruse,1  and 
known  as  the  Streptococcus  lacticus,  is  almost  always 
present  and  appears  to  be  identical  with  the  streptococ- 
cus of  Hirsh-Libbmann.  It  possesses  the  power  of 
coagulating  milk.  Among  the  less  constant  aerobic 
bacteria  are  the  white  staphylococci.  Sometimes  a 

1  "  Das  Verhaltnis  der  Milchsaurebakterien  zum  Streptococcus 
lanceolatus  (Pneumoniecoccus,  Enterococcus,u.s.w.),"  Centralbl.  f. 
Bakt.,  1st  Abt.,  Orig.,  xxxiv,  p.  737,  1903. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT         63 

prominent  inhabitant  is  B.  cloacce,  which  is  a  more  active 
gas  former  than  B.  coli.  In  fermentation  tubes  contain- 
ing milk  it  may  induce  an  active  gas  production  and 
disruption  of  the  coagulum  which  suggest  the  action  of 
B.  aerogenes  capsulatus.  Sarcinse  are  often  found,  both 
in  the  small  and  large  intestine,  and  white  yeasts  are 
occasionally  present.  As  was  first  pointed  out  by 
Rodella,1  there  are  several  forms  of  bacteria  present  in 
the  large  intestine  which  are  capable  of  dissolving  and 
peptonizing  casein.  These  forms,  which  are  sometimes 
facultative  anaerobes,  sometimes  obligate  anaerobes,  are 
usually  distinctly  more  abundant  in  bottle-fed  children 
than  in  nurslings.  Staphylococcus  pyogenes  albus  is  one 
of  the  peptonizing  forms  bacteria  often  present  and 
possesses  the  ability  to  liquefy  both  casein  and  gelatin. 
Probably  in  the  case  of  bottle-fed  children  this  organism 
is  less  important  as  a  liquefier  than  some  of  the  faculta- 
tive and  strict  anaerobic  bacilli.2 

1  "  Ueber  die  Bedeutung  der  im  Sauglingsstuhle  vorkommenden 
Mikroorganismen  mit  besonderer  Beriicksichtigung  der  anaeroben 
Bakterien,"  Zeitschr.  f,  Hyg.,  xli,  p.  470,  1902. 

2  The  facultative  and  strict  anaerobes  are  much  more  abundant 
in  the  large  intestines  of  bottle-fed  children  than  in  the  intestines 
of  nurslings.     I  attach  especial  importance  to  the  presence  of  B. 
aerogenes  capsulatus  which,  as  already  mentioned,  is  present  in 
only  small  numbers  in  the  case  of  breast-fed  children.    The  number 
of  these  organisms  is  not  necessarily  larger  in  the  intestines  of 
children  fed  on  cow's  milk,  but  as  a  rule  even  in  children  con- 
sidered quite  normal,  their  number,  though  still  small,  is  greater 
than  in  the  case  of  nurslings.     As  compared  with  the  number  pres- 
ent in  the  faeces  of  adults  these  bacteria  are  few.     Another  an- 
aerobic organism  which  is  sometimes  found  is  the  motile  butyric 
acid  bacillus  of  Schottenfroh  and  Grassberger.     Furthermore,  B. 
putrificus  can  be  found  in  some  instances  in  the  stools  of  bottle- 


64        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

Products  of  Decomposition  in  the  Intestinal  Tract  of 
Bottle-fed  Children.  —  It  has  already  been  pointed  out 
that  the  products  of  intestinal  decomposition  in  normal 
nurslings  are  remarkably  small  in  amount  when  we 
consider  the  large  numbers  of  bacteria  that  inhabit  the 
lower  part  of  the  intestinal  tract.  Almost  the  same  thing 
holds  true  of  the  intestinal  tract  of  bottle-fed  children. 
If  we  make  extracts  of  the  contents  of  any  portion  of  the 
large  intestine  from  a  normal,  bottle-fed  child,  we  find 
by  the  most  delicate  methods  merely  a  trace  of  indol, 
or  even  no  trace  at  all.  Traces  of  skatol  are  much  less 
frequent  than  traces  of  indol.  Corresponding  to  the 
fact  that  indol  is  in  health  always  slight  in  amount  and 
frequently  absent,  is  the  observation  that  aqueous 
extracts  from  any  part  of  the  contents  of  the  krge  in^ 
testine  give  no  reaction  with  an  acid  solution  of  dimeth- 
ylamidobenzaldehyde.  It  will  be  shown  when  dealing 

fed  children,  but  their  number  is  usually  small  and  their  presence 
inconstant.  The  bacillus  of  malignant  O3dema  has  also  been  found 
in  the  stools  of  children  fed  on  cow's  milk,  but  it  is  likewise  incon- 
stant, and  I  believe  ordinarily  of  little  physiological  importance. 
The  anaerobes  just  mentioned  —  the  motile  butyric  acid  bacillus, 
B.  aerogenes  capsulatus ,  B.  putrificus,  and  the  bacillus  of  malignant 
03dema,  are  all  spore-producers,  although  they  do  not  produce 
their  spores  with  equal  readiness.  B.  aerogenes  capsulatus  indeed 
sporulates  only  under  special  conditions  and  probably  seldom  in 
the  intestinal  tract  of  a  normal  bottle-fed  child.  The  number  of 
spores  present  in  the  faeces  of  bottle-fed  children  who  may  be  re- 
garded as  normal  is  ordinarily  very  small  as  compared  with  the 
numbers  found  in  some  conditions  of  disease.  The  character  of 
the  spores  formed  is  at  present  uncertain;  that  is  to  say,  it  is 
difficult  to  decide  in  the  case  of  free  spores  to  what  organisms  they 
belong.  Where  sporulating  bacilli  are  present,  they  are  probably 
not  members  of  the  group  of  B.  aerogenes  capsulatus. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT         65 

with  the  contents  of  the  digestive  tract  in  adults  that  a 
strong  red  coloration  with  this  aldehyde  is  commonly 
obtained  in  persons  in  fair  health  and  that  a  moderate 
reaction  is  usual  in  persons  who  are  well.  The  reaction 
depends  in  part  on  the  presence  of  indol  and  perhaps  in 
part  also  on  the  presence  of  urobilinogen.  In  the  case 
of  a  bottle-fed  child,  there  is  usually  only  a  faint  pink 
tinge  when  the  conditions  of  the  reaction  are  such  as  will 
give  a  distinct  red  in  the  case  of  material  from  adults. 
On  standing,  however,  for  several  days,  a  blue-gray 
coloration  may  set  in,  the  nature  of  which  is  not  at 
present  clear. 

If  we  acidify  a  watery  suspension  made  from  any  por- 
tion of  the  contents  of  the  intestinal  tract,  we  find  that  a 
moderate  amount  of  volatile  acid  is  obtained  in  the  dis- 
tillate. The  molecular  weight  of  such  acids  lies  usually 
between  sixty  and  sixty-five;  that  is  to  say,  it  corre- 
sponds closely  to  the  molecular  weight  for  acetic  acid. 
There  is  no  doubt  that  acetic  acid  forms  by  far  the  larger 
amount  of  the  acids  normally  present  in  the  distillate 
prepared  as  just  mentioned.  The  presence  of  acetic  acid 
rather  than  of  higher  fatty  acids  indicates  that  such 
bacterial  processes  of  decomposition  as  occur  within  the 
intestinal  tract  are  of  a  fermentative  rather  than  of  a 
putrefactive  nature.  It  is  a  fact  of  interest  that  if  we 
take  the  intestinal  contents  of  a  normal  horse  and  make 
a  distillation  for  the  determination  of  the  volatile  acids 
present,  this  volatile  acid  also  corresponds  in  molecular 
weight  to  the  figures  corresponding  to  acetic  acid.  The 
same  thing  is  true  of  young  pigs.  These  facts,  and  others 


66         INFECTIONS  OF  THE  DIGESTIVE  TRACT 

which  might  be  brought  forward,  plainly  point  to  the 
presence  of  acetic  acid  fermentation  as  a  normal  process 
in  many  healthy  animals.  If  the  material  employed  be 
distilled  after  the  addition  of  alkali  instead  of  acid,  one 
obtains  the  volatile  alkali;  namely,  ammonia.  The 
quantity  of  ammonia  found  is  moderate  and  about  suf- 
fices to  neutralize  the  acetic  acid  which  is  present. 

Action  of  the  Mixed  Fcecal  Flora  upon  Various  Media. 
-  As  already  mentioned  in  describing  the  action  of  the 
mixed  faecal  flora  from  the  nursling,  the  products  of 
bacterial  action  are  determined  in  important  ways  by 
the  nature  of  the  medium,  and  both  their  quality  and 
quantity  are  influenced  in  important  ways  by  the  readi- 
ness with  which  bacteria  grow  upon  the  various  media. 
If  we  grow  the  mixed  flora  from  a  normal  bottle-fed  child 
upon  sugar  bouillon,  there  is  always  a  production  of  gas 
hi  the  fermentation  tube,  and  this  production  of  gas  is 
usually  greatest  in  lactose  bouillon.  A  less  production  of 
gas  is  seen  in  dextrose  and  levulose  and  the  slightest  is 
observed  in  saccharose.  By  making  strongly  alkaline 
with  sodium  hydroxide  one  may  measure  the  amount  of 
carbon  dioxide  that  has  been  formed,  and  such  observa- 
tions have  shown  that  from  one-third  to  two-thirds  of 
the  gas  produced  under  these  circumstances  is  carbon 
dioxide.  The  composition  of  the  remaining  gas  is  not 
yet  definitely  known,  but  it  consists  mainly  of  hydrogen 
and  probably  in  part  of  methane.  It  will  be  found 
on  using  litmus  paper  that  there  has  been  a  production 
of  acid  at  the  same  time  that  gas  was  produced. 
Acetone  is  not  usually  detectable  in  sugar-bouillon 


INFECTIONS  OF  THE  DIGESTIVE  TRACT         67 

cultures.  If  the  sediments  in  fermentation  tubes 
prepared  in  the  manner  just  mentioned  be  examined 
microscopically,  it  will  be  found  in  every  case  that  there 
has  been  a  fairly  abundant  growth  of  microorganisms 
of  the  B.  coli  type.  The  staphylococci  and  Gram- 
positive  diplococci  will  also  be  found  to  have  multiplied 
in  the  anaerobic  limb  of  the  tube.  As  a  rule  there  is 
little  or  no  evidence  of  the  development  of  strict 
anaerobes. 

The  gas  production  and  the  acid  formation  which  have 
been  noted  are  probably  to  be  ascribed  almost  exclusively 
to  the  action  of  organisms  of  the  B.  coli  group.  The 
presence  of  streptococcal  forms  in  abundance  appears 
to  inhibit  the  formation  of  gas,  probably  by  checking  the 
development  of  the  colon  bacilli. 

If  suspensions  of  the  mixed  flora  be  inoculated  into  the 
fermentation  tubes  containing  bouillon  without  sugar, 
the  results  of  the  bacterial  decomposition  are  different. 
Here  we  find  either  very  small  gas  production  or  none 
whatever,  and  such  acids  as  may  be  produced  are,  more- 
over, bound  by  alkali,  so  that  the  medium,  originally 
neutral,  either  remains  so  or  becomes  faintly  alkaline. 
There  is  a  moderate  production  of  ammonia.  This 
ammonia  is  united  mainly  to  acetic  acid.  There  is  also 
a  production  of  hydrogen  sulphide  under  these  circum- 
stances. Not  rarely  there  is  a  small  quantity  of  mercap- 
tan,  but  as  a  rule  the  amount  of  mercaptan  produced  is 
little  more  than  a  trace,  and  very  frequently  —  perhaps 
usually  —  it  is  wholly  absent.  The  formation  of  indol 
is  a  constant  phenomenon  on  the  bouillon  medium,  and 


68         INFECTIONS  OF  THE  DIGESTIVE  TRACT 

in  the  course  of  twenty-four  or  forty-eight  hours  a  moder- 
ate quantity  is  usually  formed.  Skatol  has  not  been 
observed,  but  traces  of  phenol  were  regularly  found. 

Although  the  putrefactive  decompositions  in  the 
intestinal  tract  are  normally  very  limited  in  both  nurs- 
lings and  bottle-fed  children,  they  are  often  somewhat 
higher,  as  the  foregoing  pages  indicate,  in  the  case  of 
breast-fed  children.  The  reasons  for  this  are  not  en- 
tirely clear. 

The  urine  of  healthy  bottle-fed  children  does  not 
differ  from  that  of  nurslings  in  any  essential  particulars. 
The  ethereal  sulphates  perhaps  tend  to  be  excreted  in 
rather  larger  amounts  in  proportion  to  the  total  nitro- 
gen and  preformed  sulphates.  Indican  is  usually  absent 
or  present  only  in  traces. 


THE  BACTERIAL  CONDITIONS  IN  THE  DIGEST- 
IVE TRACT  DURING  CHILDHOOD,  ADOLES- 
CENCE, ADULT  LIFE,  AND  SENESCENCE 

THE  bacterial  conditions  in  the  digestive  tract  between 
the  period  of  childhood  and  that  of  old  age  differ  in 
health  so  considerably  from  the  conditions  that  exist 
during  the  period  of  milk  feeding  that  they  call  for  sepa- 
rate consideration.  The  difference  depends  mainly  on 
the  character  of  the  diet,  which  grows  more  varied  at 
the  end  of  the  milk  period  and  stays  so  throughout  the 
remainder  of  life.  With  the  more  varied  diet  comes 
increased  opportunities  for  the  entry  of  many  sorts  of 
bacteria  into  the  digestive  tract.  It  is  impossible  to 
briefly  picture  the  bacterial  conditions  in  the  digestive 
tract  in  such  a  way  as  to  take  account  of  the  many 
individual  peculiarities  which  are  met,  but  fairly  typical 
descriptions  are  possible.  It  must  be  distinctly  under- 
stood that  these  descriptions  are  based  on  well-cared-for 
individuals  and  not  on  the  study  of  neglected  persons 
or  persons  following  peculiar  occupations  which  subject 
them  constantly  to  irregular  conditions  of  life. 

Period  of  Childhood  and  Adolescence.  —  The  bacterial 
conditions  in  childhood  *  and  during  adolescence  differ 
somewhat  from  those  of  later  life,  and  it  is  essential  to 
recognize  these  differences  in  any  discussion  of  such 
conditions.  During  normal  childhood  and  adolescence 


70        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

all  the  bacteria  described  as  present  in  the  tract  during 
the  period  of  bottle-feeding  are  likely  to  be  still  present, 
for  the  use  of  cow's  milk  is  generally  continued  into 
the  epoch  of  a  mixed  diet.  Microorganisms  of  the 
B.  bifidus  type  are  usually  much  less  numerous  in  the 
intestine  in  childhood  and  adolescence  than  in  the  cow's- 
milk  period,  but  other  types  of  bacteria  are  commonly 
more  numerous.  This  is  true  of  the  putrefactive  anae- 
robes, certainly  of  B.  aerogenes  capsulatus  and  probably 
of  B.  putrificus.1  Still  the  number  of  these  anaerobes 
is  small2  and  putrefactive  processes  in  the  intestine 

1  An  organism  corresponding  to  Nencki's  B.  liquefaciens  ilei 
is  usually  abundant  in  the  lower  ileum,  ascending  colon,  and  per- 
haps the  caecum.     I  have  not  yet  had  an  opportunity  to  study  the 
biochemical  characters  of  this  organism,  but  suspect  that  it  may 
be  a  vegetative  form  of  B.  putrificus. 

2  The  following  notes  relate  to  typical  microscopical  fields  pre- 
pared from  the  digestive  tract  of  a  boy  aged  fourteen  years :  — 

CASE  OF  SUDDEN  DEATH,  MALE,  MT.  14 

Autopsy  showed  heart  dilated,  aorta  1.5  cm.  in  diameter; 
stomach  intensely  congested;  intestines  normal.  The  skull  was 
not  opened.  There  was  no  history  of  infectious  disease  to  ex- 
plain the  cardiac  dilatation,  and  no  endocarditis.  No  cause  for 
this  sudden  death  was  revealed  by  the  autopsy  findings.  The 
slides  were  made  two  hours  after  death. 

Microscopical  Findings 

I.  Stomach.     Very  few  bacteria  are  seen.     There  are  small 
numbers  of  positive  diplococci,  sometimes  in  chains,  all  medium- 
sized.     A  few  short,  negative  bacilli  and  a  few  small,  negative 
diplococci  are  also  seen. 

II.  Duodenum.     There  are  a  few  positive  diplococci;    other- 
wise no  bacteria.     Considerable   masses  of   epithelial   cells   and 
very  few  small  negative  diplococci  are  found. 

III.  Jejunum.     A  few  medium-sized,  positive  diplococci  and 


INFECTIONS  OF  THE  DIGESTIVE  TRACT        71 

are  not  active.  This  is  shown  by  the  character  of  the 
urine  and  by  the  nature  of  the  decomposition  products 

negative  cocci,  ill-defined  as  regards  staining,  are  seen.  Epithe- 
lial cells  are  numerous.  The  number  of  bacteria  here  is  extremely 
small. 

IV.  Ileum.     Bacteria  are  more  numerous  here,  but  the  number 
of  varieties  is  small.     There  are  a  few  forms  resembling  B.  coli, 
short,  stout,  negative  bacilli;    also  bacilli  of  about  the  same 
width  and  three  to  four  or  five  times  the  length  of  typical  coli; 
also  a  medium-sized  or  rather  large,  positive  diplococcus  and  a 
few  small,  positive  bacilli  about  the  size  of  colon  bacilli.     The 
long,  slender,  Gram-negative  bacillus  is  rather  prominent.     Some- 
times it  takes  the  form  of  a  fairly  long  thread.     Considerable 
epithelium  is  present  in  this  section. 

V.  Caecum.     This  field  presents  an  entirely  different  picture 
from  the  preceding.     The  bacteria  are  numerous.     The  field  is 
mixed  about  evenly  as  regards  the  staining.     Negative  bacteria 
consist  of  three  forms  —  small  diplococci  which  are  moderately 
numerous;    short  bacilli,  suggesting  colon  bacilli  in  the  typical 
form;   slender,  negative  bacilli,  more  slender  than  colon  and  two 
or  three  times  as  long,  sometimes  in  threads.     The  positive  forms 
consist  of  oval  diplococci  medium-sized,  occasionally  large,  single, 
oval  cocco-bacilli,  a  few  forms  suggesting  colon  bacilli  (but  these 
are  not  numerous)  and  a  very  few  organisms  the  size  and  form  of 
B.  aerogenes  capsulatus,  though  tending  to  be  a  little  small  for  this 
organism ;  and  a  few  positive  bacilli  of  this  type  containing  spores 
located  between  the  middle  and  end.     No  free  spores  are  observed. 
The  rather  long,  stout  negative  bacilli  observed  at  higher  levels 
are  also  seen  occasionally.     There  are  a  few  slender,  negative 
bacilli  showing  irregularities  in  staining;    that    is,    "punctate" 
bacilli. 

VI.  Sigmoid  flexure.     Bacteria  are  numerous.    The  negative 
forms  are  more  prominent  than  in  the  last  level.     Organisms  of 
the  colon  type  are  numerous,  as  are  also  slender,  negative  bacteria. 
Positive  diplococci  are  considerably  less  numerous  than  in  higher 
levels.     There  are   moderate   numbers  of  organisms  suggesting 
capsulatus,  but  their  number  is,  however,  very  small  in  comparison 
with  the  total  number  of  bacteria.      Spore-holders  are  not  seen, 
nor  are  free  spores. 

VII.  Rectum.  The  fields  are  mixed.   Colon  bacilli  are  numerous, 


72        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

in  the  faeces.  Indol  and  phenol  are  found  in  the  faeces 
in  only  very  small  quantities  —  a  few  milligrams  in 
one  hundred  grams  of  the  moist  faeces.  Frequently, 
indeed,  only  a  trace  of  indol  is  detectable  in  the  intestinal 
contents.  The  character  of  the  urine  as  regards  putre- 
factive products  corresponds  to  the  faeces.  The  ethereal 
sulphates  are  low  in  proportion  to  the  preformed,  and 
there  is  little  or  no  indican  in  the  urine.  There  is  also 
little  phenol.  The  reaction  with  dime  thy  lamidobenz- 
aldehyde  is  slight  or  moderate.  Frequently  it  is  so 
slight  that  its  existence  is  questionable.  During  a 
period  of  temporary  digestive  derangement  the  ethereal 
sulphates  may  show  a  considerable  increase,  and  indican 
may  be  present,  but  as  the  derangement  subsides  the 
urinary  indications  of  putrefactive  decomposition  in 
the  intestine  likewise  grow  less  and  gradually  fall  back 
to  the  previously  existing  normal  level. 

Period  of  Adult  Life.  —  During  adult  life  factors 
usually  enter  into  the  lives  of  human  beings  which  are 
not  without  influence  upon  the  bacterial  conditions 
that  prevail  in  the  stomach  and  intestine.  Great 
differences  exist  in  the  habits  of  different  persons  at 
this  time  of  life,  and  these  differences  are  in  a  degree 
reflected  hi  the  nature  of  the  bacterial  processes  that 

as  are  also  slender,  negative  bacilli.  There  are  moderate  numbers 
of  positive  diplococci  and  diplobacilli.  Organisms  of  the  capsulatus 
type  are  a  little  more  numerous  than  at  the  last  level.  There  are 
a  very  few  free,  oval  spores,  and  a  few  spore-holding  bacilli,  very 
much  enlarged,  suggesting  clostridia.  There  are  also  some  few 
slender  Gram-positive  bacilli  about  the  length  of  B.  aerogenes 
capsidatas  or  longer,  but  about  one-half  the  diameter  of  capsulatus. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT        73 

hold  sway  in  the  digestive  tract.  In  adult  life  the 
individual  experiences  new  responsibilities,  new  ambi- 
tions, new  dangers,  an  enhanced  emotional  life,  and  in 
very  many  instances  a  marked  change  in  the  direction 
of  more  sedentary  habits  incidental  to  a  larger  proportion 
of  indoor  life.  The  dietary  is  apt  to  undergo  an  altera- 
tion in  the  direction  of  increased  and  frequently  injudi- 
cious liberty  and  the  use  of  tea  and  coffee,  also  the  use  of 
tobacco  and  alcoholic  drinks  is  either  increased  or  begun. 
For  a  time  these  influences  may  not  make  themselves 
definitely  felt,  but  sooner  or  later  they  lead  to  slight 
derangements  of  digestion  which  manifest  themselves 
clinically.  There  are  of  course  the  greatest  individual 
differences  in  respect  to  these  manifestations.  One 
sometimes  meets  with  persons  more  than  fifty  years 
of  age  in  whom  the  bacterial  conditions  in  the  intes- 
tine do  not  differ  materially  from  those  observed  dur- 
ing the  period  of  normal  adolescence.  These  persons 
are  usually  well  nourished,  muscularly  strong,  and  capa- 
ble of  sustained  mental  and  muscular  work.  They  have 
a  high  percentage  of  hemoglobin  and  their  red  blood 
cells  approximate  the  upper  physiological  limit  in  regard 
to  number.  The  volume  of  blood  is  large.  These 
persons  are  remarkably  free  from  nervous  disturbances, 
even  under  trying  conditions  of  work.  They  generally 
have  at  their  disposal  a  surprising  amount  of  reserve 
energy. 

These  are,  however,  exceptional  instances  of  robust 
health.  A  large  portion  of  the  population  in  the  United 
States  presents  different  physical  conditions  by  the  time 


74        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

they  reach  the  fiftieth  year  of  life,  although  they  are 
in  no  sense  in  a  state  of  invalidism.  They  are  able  to  do 
large  amounts  of  work  without  excessive  fatigue  and 
most  of  the  time  they  feel  well.  While  in  such  persons 
the  faecal  flora  shows  nothing  striking,  it  is  usually  not 
difficult  to  demonstrate  that  the  number  of  putrefactive 
anaerobes  in  the  intestine  is  larger  than  is  the  case  with 
healthy  individuals  in  the  period  of  adolescence.  The 
presence  of  B.  aerogenes  capsulatus  can  be  determined 
by  anaerobic  plating  in  blood-agar,  and  the  number  of 
colonies  will  be  found  ordinarily  to  exceed  the  number 
obtainable  from  the  faeces  in  the  earlier  period  of  life. 
B.  putrificus  may  also  be  moderately  abundant.  The 
colon  bacilli  are  well  represented.  The  urine  shows  the 
presence  of  a  slightly  larger  amount  of  ethereal  sulphates 
than  is  ordinarily  found  in  earlier  life.  The  ratio  of 
ethereal  to  preformed  sulphates  varies  from  1 : 8  to 
1 : 12  most  of  the  time.  A  little  indican  is  of  frequent 
occurrence,  and  not  rarely  the  reaction  is  strong  with 
Obermeyer's  reagent  —  not  regularly  strong,  perhaps, 
but  frequently  so  for  a  few  days  at  a  time.  The  phenol 
excretion  may  also  be  a  little  greater  than  that  noted 
during  earlier  life. 

In  short,  then,  we  find  in  middle  life  a  large  number  of 
persons  whose  health  is  good  or  fair,  but  in  whom  the 
putrefactive  processes  in  the  intestine  are  distinctly 
more  active  than  is  the  case  with  most  younger  persons 
who  are  representative  of  normal  health.  These  persons, 
though  hi  good  health,  are  not  robust.  A  period  of  sus- 
tained hard  work  is  followed  by  considerable  and  per- 


INFECTIONS  OF  THE  DIGESTIVE  TRACT        75 

haps  annoying  mental  and  physical  fatigue.  Moreover, 
these  persons  have  found  by  experience  that  they  must 
be  more  careful  than  formerly  in  respect  to  food  and 
drink,  emotional  and  sexual  excitement,  etc.  Dining 
out  and  the  use  of  alcoholic  drinks  are  indulgences 
quickly  followed  by  unpleasant  consequences.  Physical 
exercise  out  of  doors  becomes  more  and  more  a  necessity 
to  this  group  of  individuals.  They  are  conscious  that 
it  requires  careful  living  to  keep  them  in  a  condition 
compatible  with  the  performance  of  their  duties. 

Period  of  Senescence.  —  The  age  of  an  individual 
must  be  measured  rather  by  the  physiological  potential 
of  his  cells  than  by  the  number  of  his  years.  There  are 
men  who  at  seventy  have  cells  with  functional  capacities 
superior  to  those  of  other  men  who  are  little  beyond 
forty,  and  who  show  their  superiority  in  the  ability  to 
work  without  fatigue,  to  digest  without  any  conscious- 
ness of  the  digestive  processes,  and  to  make  large  out- 
puts of  mental  and  muscular  energy  without  ill  effects. 
These  persons  retain  soft  arteries,  are  well  nourished,  and 
exhibit  little  atrophy  of  the  subcutaneous  areolar  tissues, 
and  hence  show  little  wrinkling  of  the  skin.  They  are, 
in  short,  candidates  for  an  advanced  age. 

If  we  examine  the  intestinal  bacteria  and  the  urine  of 
such  people,  we  find  conditions  wholly  in  harmony  with 
the  unusual  preservation  of  general  functional  powers 
and  with  the  freedom  from  signs  of  disordered  digestion. 
The  faeces  contain  an  abundance  of  viable  bacilli  of  the 
B.  coli  group  and  the  putrefactive  anaerobes  are  few 
in  number.  Analyses  show  the  presence  of  mere  traces 


76        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

of  indol  in  the  intestinal  contents  (perhaps  one  or  two 
milligrams  in  one  hundred  grams  faeces)  a  few  milligrams 
of  phenol,  and  no  skatol.  The  urine  is  free  from  indican 
almost  habitually,  and  only  moderate  quantities  of 
phenol  are  excreted  (twenty  to  forty  milligrams  in 
twenty-four  hours).  The  ethereal  sulphates  are  corre- 
spondingly low.  The  dimethylamidobenzaldehyde  re- 
action is  feeble  or  moderate  in  intensity. 

Persons  of  this  type  are  apt  to  die  at  an  advanced  age 
of  some  condition  apparently  quite  distinct  from  disease 
of  the  digestive  tract,  especially  thrombosis  of  cerebral 
vessels  (from  atheroma)  or  chronic  myocarditis. 

I  have  not  had  a  wide  experience  in  the  careful  study 
of  the  bacterial  conditions  in  persons  above  sixty-five 
years  of  age,  but  believe  it  safe  to  say  that  a  large  majority 
of  such  persons  (perhaps  seventy  per  cent,  of  the  popula- 
tion in  the  United  'States  above  this  age)  give  evidence 
of  distinct  putrefactive  processes  in  the  digestive  tract. 
These  processes  are  in  many  instances  characterized  by 
their  mildness.  But  if  we  compare  these  mild  processes 
of  putrefaction  with  those  existing  in  the  majority  of 
persons  under  twenty  years  of  age,  we  find  a  distinct 
difference  between  the  two.  I  think  it  quite  clear  that 
the  conditions  in  youth  are  much  more  close  to  the  ideal 
physiological  state  of  infancy  and  childhood  than  are 
those  of  senility.  The  difference  lies  mainly  in  the 
direction  of  the  greater  abundance  of  putrefactive 
bacteria  in  old  age,  but  with  this  there  is  apt  to  be  some 
diminution  in  the  number  of  typical  colon  bacilli,  if 
we  may  form  a  judgment  on  this  point  from  the  appear- 


INFECTIONS  OF  THE  DIGESTIVE  TRACT         77 

ance  of  the  microscopical  fields  and  the  gas  production 
in  the  fermentation  tubes.  These  conditions  of  bacterial 
activity  in  the  period  of  senility  are  like  those  which 
were  just  described  a&  being  common  in  people  about  the 
age  of  fifty.  The  main  difference  between  the  putrefac- 
tive conditions  found  at  fifty  and  at  seventy  is  that  at 
the  latter  period  they  are  a  little  more  marked  in  their 
intensity  and  affect  a  much  larger  proportion  of  the  pop- 
ulation. The  subjects  in  question  at  this  later  period 
of  life  are  not  ill,  but  in  order  to  keep  fairly  well  have  to 
be  very  careful  as  to  their  habits  of  living.  They  are 
moderately  anaemic  and  easily  develop  slight  disorders 
of  digestion.  They  weigh  less  than  formerly,  and  though 
they  may  still  be  well  nourished  in  appearance,  are  con- 
scious of  losing  strength  from  year  to  year.  They  are 
undergoing  what  is  usually  regarded  as  normal  involution. 
Thus  it  is  clear  that  there  exists  a  distinct  difference 
between  normal  childhood  and  adolescence  on  the  one 
hand  and  normal  old  age  on  the  other  in  respect  to  the 
intensity  of  the  putrefactive  processes  that  go  on  in  the 
digestive  tract.  The  origin  and  precise  significance  of 
this  difference  are  at  present  not  clear.  It  appears 
likely  that  the  tendency  to  an  increasing  degree  of  putre- 
factive decomposition  in  the  intestine  is  connected  with 
the  repeated  but  not  necessarily  severe  derangements 
of  intestinal  function  that  are  experienced  from  time  to 
time  by  most  individuals.  In  the  course  of  these  acute 
derangements,  there  is  frequently  an  increased  opportu- 
nity for  the  development  of  putrefactive  anaerobes,  and 
it  is  possible  that  owing  to  slight  but  persistent  damage 


r&        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

to  the  epithelial  and  other  structures  of  the  intestinal 
mucous  membrane,  these  anaerobes  are  gradually  afforded 
more  and  more  favorable  opportunities  for  their  growth. 

As  to  the  relation  between  the  relatively  active  anaerobic 
life  in  the  intestine  during  senility  and  the  development 
of  the  involutional  alterations  in  the  tissues,  it  is  difficult 
to  formulate  an  opinion.  Many  factors  may  doubtless 
enter  into  the  production  of  these  cellular  alterations,  and 
it  is  difficult  to  assign  to  each  of  these  its  just  position. 
One  statement  may,  however,  be  confidently  made: 
the  onset  of  senility  may  be  distinctly  accelerated  through 
the  development  of  intestinal  infections  in  which  the 
putrefactive  anaerobes  are  prominently  represented. 
I  have  observed  this  in  cases  where  it  has  appeared  to 
me  a  certainty  that  other  toxic  causes  of  premature 
senility  could  be  excluded. 

The  view  that  intestinal  infections  stand  in  a  causative 
relation  to  old  age  is  by  no  means  new.  It  has  been 
advanced  by  Metchnikoff  on  several  occasions.  It  is 
probable  that  the  "wild  races"  of  bacteria  of  which 
he  speaks  as  responsible  for  senile  changes  consist  largely 
of  putrefactive  microorganisms.  I  do  not  know  that 
Metchnikoff  has  singled  out  any  definite  group  of  micro- 
organisms as  especially  concerned.  I  am  inclined  to  give 
prominence  to  B.  aerogenes  capsulatus  as  the  most  impor- 
tant factor  in  the  production  of  the  putrefactive  decom- 
positions of  advanced  age.  It  is  extremely  probable 
that  persons  with  apparently  equal  numbers  of  gas- 
bacilli  in  the  intestinal  tract  do  not  necessarily  suffer  an 
equal  degree  of  harmful  influence  from  their  putrefactive 


INFECTIONS  OF  THE  DIGESTIVE  TRACT         79 

products.  Some  races  of  the  gas-bacillus  are  much  less 
pathogenic  for  animals  than  others,  and  these  differences 
in  pathogenicity  may  be  of  considerable  significance  to 
human  beings  harboring  them. 


CHARACTERS  OF  THE  BACTERIAL  FLORA  OF 
CARNIVOROUS  AND  OF  HERBIVOROUS  ANI- 
MALS 

IN  the  course  of  the  study  of  anaerobes  of  the  human 
intestine  it  appeared  desirable  to  learn  something  about 
the  characters  of  the  bacterial  flora  inhabiting  the  large 
intestine  of  various  domestic  and  wild  animals.  It 
was  noticed  that  in  the  dog,  which  is  frequently  exclu- 
sively carnivorous,  the  intestinal  contents  often  showed 
the  presence  of  large  numbers  of  spores,  spore-bearing 
bacilli,  and  vegetative  forms  of  anaerobes.  The  numbers 
present  in  the  faeces  were  noted  to  be  especially  large  in 
some  animals  which  had  been  exclusively  fed  on  meat. 
A  study  of  a  grown  cat  fed  upon  raw  meat  showed  the 
presence  of  Gram-positive  vegetative  anaerobes  from 
one  end  of  the  digestive  tract  to  the  other.  Flora  derived 
from  the  stomach,  small  intestine,  and  large  intestine 
were  inoculated  and  grown  in  bouillon  flasks  and  showed 
an  abundant  production  of  methyl  mercaptan  as  well 
as  of  hydrogen  sulphide.  The  numbers  of  colon  bacilli 
present  in  this  case  were  relatively  small  as  compared 
with  the  anaerobes.  The  study  of  the  colonies  obtained 
on  anaerobic  plates  showed  that  a  large  portion  of  the 
organisms  present  in  the  intestinal  tract  were  B.  aero- 
genes  capsulatus.  Intravenous  infusion  of  these  organisms 

80 


INFECTIONS  OF  THE  DIGESTIVE  TRACT        81 

into  a  rabbit  which  was  afterwards  killed  and  incubated 
showed  in  a  high  degree  the  typical  gas  formation.1 

Observations  on  other  cats  showed  the  presence  of 
considerable  numbers  of  spore-holding  bacilli  and  free 
spores,  sometimes  in  chains,  in  addition  to  vegetative 
forms  of  anaerobes.  The  position  of  these  spores  and 
spore-holding  bacilli  has  not  been  established  in  a  bacte- 
riological sense.  Observations  were  also  made  upon  the 
intestinal  contents  of  the  wolf,  tiger,  and  lion.  Several 
different  tigers  were  studied,  and  the  observations  were 
not  confined  to  the  examination  of  one  lion  and  one  wolf. 
The  material  from  the  lion  showed  the  presence  of  many 
free  spores.  It  also  showed  the  presence  of  considerable 
numbers  of  Gram-positive  bacilli,  suggesting  B.  aero- 
genes  capsulatus.  Gram-stained  preparations  from  wolves 
showed  pictures  similar  to  those  observed  in  the  lion 
except  that  the  spore-holding  bacilli  were  more  numerous. 
The  findings  in  the  case  of  supposedly  healthy  tigers 
were  not  essentially  different  from  those  in  the  case  of 
the  wolf  and  lion.  In  the  case  of  one  tiger,  suffering 
from  osteomalacia,  greatly  impaired  nutrition,  and  loss 
of  strength,  the  microscopical  fields  derived  from  several 
different  samples  of  faeces  revealed  the  presence  of  im- 
mense numbers  of  free  spores  and  smaller  numbers  of 
immature  Gram-negative  spore-holding  bacilli.  These 
spores  developed  into  organisms  which  possessed  all 
the  generally  known  cultural  and  biochemical  characters 
of  B.  aerogenes  capsulatus,  including  the  ability  to  develop 

JThe  method  by  which  these  incubation  experiments  were 
carried  out  is  explained  on  p.  84. 


82        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

a  high  grade  of  gas  formation  in  rabbits  injected  and 
incubated. 

It  was  found  that  bouillon  cultures  of  the  mixed  faecal 
flora  from  the  lion,  tiger,  wolf,  and  cat  all  developed 
quickly  a  sufficient  quantity  of  methyl  mercaptan  to  give 
a  prompt,  strong  reaction  with  isatin  in  sulphuric  acid. 

Experiments  were  made  with  the  mixed  fsecal  flora 
from  these  carnivorous  animals  to  determine  their  patho- 
genicity  when  injected  into  the  subcutaneous  connective 
tissue.  It  would  have  been  better  to  have  worked 
with  pure  cultures  of  the  anaerobes  in  question,  but 
opportunity  has  not  yet  arisen  to  isolate  them.  The 
result  of  the  inoculations  into  guinea-pigs  was  the  same 
in  each  instance.  The  animals  died  within  twenty- 
four  hours  and  usually  in  fifteen  to  eighteen  hours. 
At  autopsy  the  subcutaneous  connective  tissues  were 
haemorrhagic,  oedematous,  and  showed  necrotic  changes 
which  extended  in  some  instances  to  the  muscles.  Gas 
formation  was  not  usually  noted  as  a  prominent  feature. 
These  pathological  alterations  were  not  confined  to  the 
site  of  inoculation,  but  had  extended  to  the  subcutaneous 
connective  tissues  throughout  the  body  and  were  espe- 
cially pronounced  in  the  axillae  and  in  the  groin.  It  is 
unnecessary  to  enter  here  into  the  details  as  to  the 
character  of  the  organisms  recovered  from  these  lesions. 

We  may  contrast  with  these  findings  the  observations 
made  upon  herbivorous  animals,  including  the  buffalo, 
goat,  horse,  elephant,  and  camel.  In  the  case  of  the 
camel,  elephant,  and  horse  the  preponderant  bacteria 
in  the  Gram-stained  fields  were  small,  Gram-negative 


INFECTIONS  OF  THE  DIGESTIVE  TRACT         83 

organisms  which  were  regarded  as  special  forms  of  B. 
coli.  In  the  case  of  the  goat  the  fields  contained  some 
Gram-positive  bacteria,  and  of  the  Gram-negative  ones 
a  considerable  number  were  of  greater  length  than  the 
dominant  small  forms  which  were  regarded  as  belonging 
in  the  class  of  colon  bacilli.  In  the  case  of  the  buffalo, 
mixed  fields  were  found  as  regards  the  Gram-staining 
and  many  of  the  positive  organisms  were  found  to  be 
small  diplococci  and  small  bacilli.  In  none  of  these 
animals  were  seen  any  organisms  suggesting  B.  aerogenes 
capsulatus,  excepting  in  the  case  of  the  buffalo,  where 
the  number  of  bacilli  of  this  type  was  very  small.  Spore- 
holding  organisms  were  not  observed,  but  moderate 
numbers  of  free  spores  were  noticed  in  all  the  fields  except 
those  from  the  elephant.  In  the  fields  showing  the 
largest  number  of  spores  their  occurrence  was  far  less 
frequent  than  in  the  lion,  tiger,  wolf,  or  cat. 

The  mixed  flora  of  these  different  herbivorous  animals, 
grown  upon  peptone  bouillon,  failed  to  show  the  produc- 
tion of  methyl  mercaptan  excepting  in  the  case  of  the 
horse,  where  a  moderate  reaction  was  obtained. 

Observations  were  also  made  upon  the  effect  of  sus- 
pensions of  the  mixed  flora  from  herbivorous  animals 
when  injected  subcutaneously.  The  quantities  of 
suspension  employed  were  usually  about  twice  as  great 
as  in  the  case  of  the  suspensions  from  the  carnivorous 
animals.  With  the  exception  of  the  suspensions  obtained 
from  the  horse,  the  pathogenicity  of  these  suspensions 
was  found  to  be  slight,  the  guinea-pigs  frequently 
living  two  or  three  days  or  entirely  recovering.  In  the 


84        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

animals  injected  with  faeces  from  the  horse  were  found 
hsemorrhagic  and  cedematous  lesions  with  necrosis, 
similar  to  those  found  in  the  carnivorous  animals. 
These  lesions  were,  however,  less  pronounced  than  hi  the 
case  of  the  suspensions  from  the  carnivorous  animals. 
In  the  case  of  the  elephant  a  considerable  quantity 
of  fibrinous  exudate  was  found  about  the  point  of  in- 
oculation. No  oedema  or  necrotic  change  was  observed 
in  the  subcutaneous  tissues. 

A  further  confirmation  of  the  radical  differences 
existing  in  the  intestinal  tracts  of  carnivora  and  her- 
bivora  is  furnished  by  a  series  of  observations  with  the 
Welch-Nut  tall  incubation  test.  Suspensions  were  made 
from  the  fseces  of  all  the  types  of  animals  mentioned, 
and  equal  quantities  of  these  suspensions  were  infused 
intravenously  into  a  series  of  living  rabbits.  The  rabbits 
were  then  quickly  killed  and  incubated.  On  examination 
after  twenty-four  hours  it  was  found  that  all  the  rabbits 
infused  with  suspensions  from  carnivora  showed  in  an 
extreme  degree  the  characteristic  putrefactive  changes 
hi  the  liver,  cellular  tissues,  etc.,  induced  by  pure  cul- 
tures of  B.  aerogenes  capsulatus  or  of  the  bacillus  of 
symptomatic  anthrax.  The  rabbits  infused  with  sus- 
pensions made  from  the  fseces  of  the  herbivora  showed 
similar  but  very  much  slighter  changes  in  each  case. 
The  results  for  each  group  of  animals  separated  the  her- 
bivora sharply  from  the  carnivora.  Examination  of  the 
livers  showed  the  number  of  bacteria  hi  the  carnivorous 
series  to  be  many  times  greater  than  in  the  herbivorous 
series.  The  microorganisms  were  regarded  as  being 


INFECTIONS  OF  THE  DIGESTIVE  TRACT        85 

almost  certainly  B.  aerogenes  capsulatus  on  account  of 
their  morphology  and  failure  to  sporulate.  The  bacilli 
of  symptomatic  anthrax  readily  sporulate  in  the  incu- 
bated rabbits.  The  gas-bacillus  (B.  aerogenes  capsulatus) 
does  not  sporulate  under  these  circumstances. 

These  differences  in  the  appearance  and  behavior 
of  the  bacteria  derived  from  typical  carnivora  and 
herbivora  suggest  that  the  habit  of  living  upon  a  diet 
consisting  exclusively  of  raw  meat  entails  differences 
in  the  types  of  bacteria  that  characterize  the  contents 
of  the  large  intestine.  The  occurrence  of  considerable 
numbers  of  spore-bearing  organisms  in"  the  carnivora 
points  to  the  presence  of  anaerobic  putrefactive  forms 
in  great  numbers.  The  results  of  subcutaneous  inocula- 
tions into  guinea-pigs  bear  out  this  view  and  indicate 
that  the  numbers  of  organisms  capable  of  producing  a 
hsemorrhagic  oedema  with  tissue  necrosis,  with  or  without 
gas  production,  are  very  considerable.  Unfortunately 
the  data  pertaining  to  the  biological  properties  of  these 
pathogenic  anaerobes  are  at  present  insufficient  to  permit 
us  to  classify  them  or  to  say  more  of  their  nature  than 
that  they  are  organisms  representative  of  a  definite 
group  of  putrefactive  anaerobes  which  make  butyric 
acid  and  hydrogen  and  exert  a  peptonizing  action  upon 
living  tissues.  Nevertheless  the  observations  here  re- 
corded are  of  much  interest  in  relation  to  the  bacterial 
processes  and  nutrition  of  herbivorous  *  as  distinguished 
from  carnivorous  animals,  and  are  significant  furthermore 

1  Many  of  the  herbivora  yielded  mixed  flora  incapable  of  making 
gas  on  dextrose  bouillon. 


86        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

for  the  interpretation  of  bacterial  conditions  found  in 
man.  The  question  arises  whether  the  abundant  use  of 
meat  over  a  long  period  of  time  may  not  favor  the  devel- 
opment of  much  larger  numbers  of  spore-bearing  putre- 
factive anaerobes  in  the  intestinal  tract  than  would  be  the 
case  were  a  different  type  of  proteid  substituted  for  meat. 
Inquiries  made  of  Dr.  Blair,  the  pathologist  in  the  New 
York  Zoological  Gardens,  elicited  the  fact  that  while, 
upon  the  whole,  the  carnivorous  animals  are  apt  to  live 
somewhat  longer  than  the  herbivorous  animals  of  about 
equal  size,  the  carnivora  are  much  more  likely  to  develop 
conditions  of  advanced  anaemia  in  the  later  years  of  their 
lives  than  is  the  case  with  the  herbivora.  Dr.  Blair 
states  that  it  is  usual  in  the  later  years  of  life  for  the  car- 
nivora to  show  a  much  diminished  volume  of  blood  and 
at  least  a  moderate  fall  in  the  haemoglobin.  Instances 
are  stated  to  be  not  uncommon  in  which  a  pernicious 
type  of  anaemia  has  developed  in  the  carnivora.  On 
the  contrary,  among  the  herbivora  it  is  said  that  pro- 
nounced anaemias  are  vejy  occasional.  The  examples 
of  severe  anaemia  encountered  among  the  herbivora 
were  said  by  Dr.  Blair  to  be  in  nearly  all  instances 
referable  to  gross  animal  parasites. 

INFLUENCE   OF   FOOD   ON    HUMAN    BACTERIAL    FLORA    OF 
THE   DIGESTIVE   TRACT 

Surprisingly  little  is  known  about  the  influence  of 
different  classes  of  food  upon  the  nature  of  the  micro- 
organisms in  the  digestive  tract.  It  is  evident  that 
this  subject  is  one  that  deserves  the  most  careful  kind 


INFECTIONS  OF  THE  DIGESTIVE  TRACT        87 

of  study  by  means  of  modern  methods.  That  a  knowl- 
edge of  the  influence  of  different  foods  upon  the  flora 
in  health  and  disease  would  not  only  be  of  great  bio- 
logical interest  but  would  also  give  many  indications 
of  a  practical  sort  for  the  use  of  different  types  of 
foods  in  pathological  conditions,  requires  no  argument. 
Some  observations  have  been  recorded  upon  the  influ- 
ence of  food  which  have  led  to  the  conclusion  that  there 
is  little  difference  between  a,  diet  consisting  of  vegetable 
food  on  the  one  hand  and  a  mixed  diet  with  abundance 
of  meat  on  the  other.  The  methods  employed  for  de- 
termining the  presence  of  differences  in  the  character 
of  the  flora  were,  however,  so  crude  that  the  work  in 
question  cannot  be  regarded  as  in  any  manner  conclusive. 
I  have  observed  that  the  number  of  Gram-positive 
organisms  in  the  faecal  fields  was  much  increased  when 
an  adult  subject  who  had  previously  been  on  a  mixed 
diet  began  to  live  on  a  dietary  consisting  almost  exclu- 
sively of  meat.  The  microscopical  appearances  indicated 
that  an  increase  in  the  number  of  putrefactive  anaerobes 
was  largely  responsible  for  the  change  from  a  mixed 
faecal  field  to  one  which  was  dominantly  Gram-positive. 
In  this  connection  I  think  the  observation  noteworthy 
that  the  intestinal  contents  of  animals  living  on  a  diet 
of  raw  meat  tend  to  give  mixed  or  dominantly  Gram- 
positive  fields,  whereas  similar  material  from  herbivo- 
rous animals  tends  to  give  fields  in  which  Gram-negative 
organisms  are  predominant.  As  mentioned  in  connection 
with  the  discussion  of  the  faecal  flora  in  herbivorous 
animals  as  compared  with  carnivorous  animals,  there  is 


88        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

a  great  difference  in  the  numbers  of  anaerobes  in  the  two 
groups,  the  number  of  these  organisms  being  greater 
in  the  case  of  the  carnivora.1  Some  observations  of 
interest  on  the  flora  of  dogs  we  owe  to  Lembke,2  who 
found  distinct  differences  between  the  flora  after  a  diet 
of  bread  and  after  one  of  meat.  Of  especial  interest  is 
the  fact  that  a  bread  diet  rendered  the  faeces  much 
richer  in  anaerobes  than  did  a  diet  of  meat.  The  bacteria 
observed  upon  the  diet  containing  a  great  abundance  of 
fat  resembled  closely  those  noted  on  a  bread  diet.  The 
changes  which  are  induced  by  alteration  in  the  diet  are 
said  by  Lembke  to  be  generally  of  a  temporary  sort. 
On  this  subject  he  speaks  hi  the  following  way:  "If 
the  diet  is  changed,  there  appear  on  the  fsecal  plates 
new  colonies  of  the  most  varied  sort.  In  the  course  of  a 
few  days  these  are  materially  reduced  and  the  colonies 
of  B.  coli  again  gain  the  upper  hand."  It  appears  that 
with  almost  any  change  in  diet  new  varieties  of  bacteria 
are  introduced  in  large  numbers  and  somewhat  obscure 
the  predominance  of  the  colon  bacilli  in  the  fsecal 
fields.  Very  soon,  however,  the  colon  bacilli  regain  their 
original  predominance,  doubtless  owing  to  the  fact  that 
they  are  better  able  to  adapt  themselves  to  the  nutrient 
conditions  than  are  the  facultative  forms  which  have 
been  introduced.  Lembke  states  that  if  one  limits  the 
entry  of  bacteria  by  sterilization  of  the  diet,  the  foreign 

1  Escherich  found  in  a  young  dog  whose  milk-fseces  flora  was 
very  similar  to  that  of  normal  nurslings,  that  after  a  pure  meat 
diet  there  was  only  an  extremely  small  proportion  of  colon  bacilli, 
whereas  there  appeared  large  numbers  of  liquefying  colonies. 

2  "Beitrag  zur  Bacterienflora  des  Darms,"  Archiv  f.  Hyg.,  xxvi, 
p.  325,  1896. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT        89 

types  of  microorganisms  after  a  time  disappear  and  the 
plates  show  exclusively  colonies  of  the  colon  bacillus 
and  B.  lactis  aerogenes  in  almost  pure  culture.  On  the 
other  hand,  there  is  good  evidence  that  the  Gram-nega- 
tive bacilli  of  the  f  seces  may  be  temporarily  replaced  by 
feeding  Gram-positive  acidophile  bacteria. 

It  appears  probable  that  in  considering  the  influence 
of  foods  upon  the  flora  of  the  intestinal  tract  one  should 
take  into  account  .the  factor  of  rapid  digestion  and 
absorption  in  the  upper  part  of  the  digestive  tract. 
For  example,  in  cases  where  a  patient  takes  daily  a  large 
quantity  of  meat  which  is  imperfectly  masticated,  there 
is  much  more  opportunity  for  the  development  of  pu- 
trefactive anaerobes  in  the  lower  part  of  the  intestine 
than  if  the  same  quantity  of  meat  is  thoroughly  sub- 
divided by  mastication.  I  believe  also  that  the  influence 
of  diet  must  be  largely  modified  by  the  character  of  the 
dominant  organisms  in  the  intestinal  tract  and  that  this 
influence  may  come  to  the  front  in  a  telling  way  in  cases 
of  chronic  infections  of  the  large  intestine. 

THE   REDUCING   ACTION   OF  MEAT 

In  the  study  of  the  anaerobic  conditions  that  prevail 
in  the  digestive  tract  it  is  important  to  recognize  every 
factor  that  may  enter  into  the  production  of  anaerobic 
conditions  there.  It  seems  extremely  probable  that 
different  articles  of  food  have  a  different  significance  in 
respect  to  their  influence  on  the  presence  or  absence  of 
oxygen  in  the  digestive  tract.  It  is  known  that  fresh 
tissues  of  animals  exert  a  considerable  degree  of  reduc- 


90        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

ing  power  and  that  this  reducing  power  is  much  more 
active  in  general  than  the  reducing  action  of  vegetable 
cells.  If  one  places  in  a  cylinder  or  flask  a  quantity  of 
finely  divided  fresh  muscle  of  liver  from  a  mammal  and 
immerses  this  material  in  a  dilute  solution  of  methylene 
blue,  under  such  conditions  that  oxygen  from  the  air  is 
largely  excluded  from  the  region  occupied  by  the  divided 
tissues,  it  is  soon  noticeable  that  the  blue  color  begins  to 
disappear,  owing  to  the  conversion  of  methylene  blue 
into  leucomethylene  blue.  The  reducing  action  of  fresh 
liver  has  been  successfully  employed  by  Professor  Theo- 
bald Smith  in  rendering  the  closed  arm  of  the  fermen- 
tation tube  more  strictly  anaerobic  and  thus  facilitating 
the  growth  of*  certain  strictly  anaerobic  bacteria.  With 
these  facts  in  mind  one  naturally  asks  whether  the  use 
of  large  quantities  of  raw  muscle  may  not  considerably 
aid  in  the  production  of  anaerobic  conditions  in  the  di- 
gestive tract.  In  the  case  of  carnivorous  animals  living 
on  raw  meat  there  seems  little  doubt  that  anaerobic 
conditions  may  exist  throughout  the  digestive  tract,  and 
I  think  it  probable  that  the  reducing  action  of  the  meat 
in  the  upper  part  of  the  tract  may  materially  contribute 
to  diminish  the  quantity  of  oxygen  carried  into  the  di- 
gestive tract.  Even  in  the  case  of  man  this  factor  is  one 
which  cannot  be  entirely  ignored.  Although  human 
beings  in  civilized  countries  for  the  most  part  eat  their 
meat  after  it  has  been  subjected  to  cooking,  there  are 
many  instances  in  which  large  quantities  of  raw  or  nearly 
raw  meat  are  eaten.  Moreover,  meat  that  has  been 
slightly  cooked  still  retains  considerable  reducing  power. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT         91 

How  far  the  excessive  use  of  meat  that  is  raw  or 
slightly  cooked  may  influence  the  production  of  anaerobic 
states  in  the  digestive  tract  it  is  at  present  impossible 
to  say,  but  it  seems  not  unlikely  that  there  are  cases 
of  excessive  intestinal  putrefaction  dependent  on  the 
excessive  activity  of  anaerobes  hi  which  the  conditions 
of  anaerobiosis  are  distinctly  favored  by  excessive  meat 
eating. 

THE    INFLUENCE    OF    THE    EPITHELIAL    CELLS    LINING 
THE    DIGESTIVE   TRACT 

We  know  at  present  little  of  the  influence  of  changes 
in  the  epithelia  lining  the  digestive  tract  upon  the 
physiology  and  pathology  of  the  human  organism. 
There  are,  however,  certain  general  considerations  that 
require  mention  here.  It  may  be  safely  assumed  that 
every  cell  possesses  a  certain  life  potentiality ;  that  is, 
has  an  inherent  capacity  if  undisturbed  by  injurious 
agencies  to  live  a  certain  period  of  time.  Every 
epithelial  cell  of  the  digestive  tract  doubtless  pos- 
sesses a  high  capacity  for  reproduction.  This  power 
must,  nevertheless,  be  a  limited  one,  and  if  the  cells  of 
the  digestive  tract  be  injured  by  too  many  demands 
upon  them,  they  may  fail  after  a  time  to  reproduce 
normally.  Superficial  cells  which  have  under  these 
circumstances  undergone  desquamation  are  thus  not 
so  easily  replaced.  It  may  happen  that  in  some  portions 
of  the  digestive  tract  the  epithelial  layer  is  much  thinner 
than  normal,  owing  to  excessive  desquamation  as  com- 
pared with  their  power  of  reproduction.  For  example, 


92        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

we  see  in  the  case  of  Miiller's  superficial  glossitis  (geo- 
graphical tongue)  a  condition  in  which  varying  areas 
of  the  tongue  suffer  a  temporary  or  permanent  loss  of 
the  superficial  epithelial  layers.  In  many  cases  of  chronic 
disorder  of  digestion  of  very  long  standing,  the  papillae  of 
the  entire  dorsal  surface  of  the  tongue  show  excessive 
desquamation  of  the  epithelium.  In  how  far  similar 
conditions  occur  in  other  parts  of  the  digestive  tract 
we  do  not  know,  but  there  is  reason  for  believing  that  in 
some  chronic  derangements  of  digestion  there  is  in  the 
stomach  and  in  the  intestinal  tract  a  similar  thinning 
of  the  epithelial  layer.  How  far  conditions  of  the  tongue 
may  be  regarded  as  an  index  to  the  conditions  in  other 
parts  of  the  digestive  tract  is  uncertain. 

Of  the  pathological  effects  of  excessive  desquamation 
of  epithelium  we  have  at  present  little  definite  knowledge. 
It  appears  reasonable  to  suppose  that  where  desquama- 
tion is  excessive  without  corresponding  reproduction  of 
epithelial  elements  there  must  be  diminished  secretion, 
provided  the  cells  in  question  take  any  part  whatever 
in  providing  a  secretion  containing  digestive  enzymes. 
It  seems  likely  also  that  the  process  involved  in  transu- 
dation  may  be  abnormal  under  conditions  in  which 
the  epithelial  layer  is  greatly  thinned.  There  are  some 
patients  in  whom  the  tongue  indicates  an  excessive 
desquamation  of  the  epithelium  and  in  whom  cathartics 
such  as  salines  no  longer  act  promptly  or  efficiently. 
It  seems  to  me  possible  that  the  not  uncommon  appear- 
ance of  a  loss  of  response  to  cathartics  may  be  connected 
with  the  partial  failure  in  function  of  the  epithelium  of  the 


INFECTIONS  OF  THE  DIGESTIVE  TRACT        93 

intestinal  tract.  The  correctness  or  incorrectness  of  this 
view  can  only  be  established  by  experimental  methods. 
Still  another  influence  of  diminished  function  in  con- 
sequence of  a  pathological  thinning  of  the  epithelial 
layers  may  be  found  in  a  diminished  capacity  on  the  part 
of  the  intestinal  epithelium  to  act  upon  products  of 
decomposition  in  the  intestine.  In  experiments  made 
many  years  ago  with  indol,  it  was  found  that  the  epithe- 
lium of  the  digestive  tract  possesses  in  a  high  degree 
the  capacity  to  bind  indol  in  such  a  way  that  this  sub- 
stance cannot  be  recovered  by  distillation.  I  think  it 
likely  that  in  cases  where  there  is  excessive  production 
and  absorption  of  indol  in  the  intestinal  tract  the  epithe- 
lium acts  as  a  protective  agency  to  the  organism  as  a 
whole.  This  action  of  the  epithelial  cells  is  certainly 
not  confined  to  indol.  It  seems  not  unreasonable  to 
suppose  that  where  the  epithelium  has  been  very  much 
thinned,  the  organism  suffers  from  the  enfeeblement  of 
this  function  incidental  to  the  loss  of  epithelium.  Here 
again  experimental  methods  should  throw  more  light 
upon  this  protective  action  of  the  intestinal  epithelium. 

THE    PERMEABILITY    OF    THE    MUCOUS    MEMBRANE    OF 
THE   INTESTINAL  TRACT   FOR   BACTERIA 

Another  function  of  the  epithelial  cells  of  the  digestive 
tract  has  to  do  with  the  protection  of  the  body  from 
the  invasion  by  bacteria  within  the  tract.  There  exists 
some  experimental  evidence  indicating  that  an  intact, 
fully  developed  layer  of  epithelium  is  an  important 
barrier  to  the  entry  of  at  least  some  kinds  of  bacteria 


94        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

into  the  mucous  membrane.  How  far  the  presence 
of  mucus  on  the  surface  of  the  epithelial  layer  is  a 
factor  in  rendering  the  mucous  membrane  impermeable 
is  still  a  question.  It  appears  from  the  work  of 
Hilgermann 1  and  others  that  the  normal  mucous 
membrane  is  much  more  permeable  to  some  bacteria 
during  the  period  of  infancy  than  in  later  life.  It  was 
found  by  Hilgermann  that  when  young  rabbits  and 
guinea-pigs  are  fed  with  tubercle  bacilli,  these  organisms 
pass  through  the  wall  of  the  stomach  and  penetrate 
the  digestive  tract  throughout  its  entire  extent.  It 
was  noticed  that  the  number  of  bacteria  passing  through 
the  small  intestine,  especially  in  its  upper  third,  was 
considerable,  whereas  the  number  which  penetrated  the 
wall  of  the  large  intestine  was  much  smaller.  In  the 
vermiform  process  the  conditions  for  the  passage  of 
tubercle  bacilli  appear  to  have  been  the  same  as  in  the 
case  of  the  small  intestine. 

Hilgermann  attempted  to  determine  what  factors 
are  concerned  in  the  passage  of  tubercle  bacilli  through 
the  digestive  tract  in  animals.  He  was  at  first  inclined 
to  regard  the  passage  as  accidental  and  due  to  small 
lesions,  but  this  view  was  abandoned  because  it  was  found 
that  the  penetration  did  not  occur  at  single  points,  but 
throughout  the  length  of  the  gastro-enteric  tract.  It 
was  found,  moreover,  that  there  is  no  evidence  of  pene- 
tration occurring  in  corjsequence  of  an  irritation  by  a 
considerable  number  of  bacteria  acting  locally.  If  this 

x"Die  Bakteriendurchlassigkeit  der  normalen  Magendarm- 
pchleimhaut  im  Saulingsalter,"  Archiv  f.  Hyg.,  liv,  p.  335,  1905. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT        95 

had  really  been  the  case,  the  bacteria  must  have  passed 
much  more  abundantly  than  they  did,  instead  of  in 
the  typical  manner  and  in  the  definite  stages  observed 
by  Hilgermann,  who  is  inclined  to  believe  with  Behring 
that  the  mucous  membrane  in  early  life  is  lacking  in 
natural  protective  substances  capable  of  hindering  the 
penetration  of  bacteria. 

Of  considerable  interest  in  connection  with  the  study 
of  the  penetration  of  the  digestive  tract  by  bacteria 
are  the  observations  of  Ficker  *  on  the  influence  of 
exhaustion  and  of  hunger  upon  the  passage  of  bacteria. 
He  calls  attention  to  the  fact  that  states  of  inanition 
favor  the  occurrence  of  infections,  especially  those  arising 
from  the  intestinal  tract,  but  that  on  the  other  hand 
the  best  nourished  and  strongest  organisms  may  show 
a  high  degree  of  sensitiveness  toward  such  infections. 
The  experiments  of  Ficker  indicate  that  excessive 
exertion  is  a  factor  which  at  times  leads  to  an  exhaustion 
which  is  a  predisposing  condition  to  infection,  especially 
in  the  case  of  typhoid  fever.  This  influence  of  exhaustion 
on  the  development  of  infection  has  been  to  some  ex- 
tent studied  by  Charrin  and  Roget  on  white  rats  which 
were  fatigued  in  a  rotating  drum.  These  animals  were 
shown  to  be  more  sensitive  to  anthrax  than  the  control 
animals.  Ficker  selected  dogs  for  his  experiments,  in- 
ducing fatigue  in  them  through  work  in  a  treadmill.  He 
found  that  a  combination  of  fasting  and  fatigue  facilitated 
in  an  extraordinary  way  the  passage  of  germs  through 

1  "  Ueber  den  Einfluss  des  Hungers  auf  die  Bakteriendurch- 
lassigkeit  des  Intestinaltraktus,"  Archiv  /.  Hyg.,  liv,  p.  354,  1905. 


96        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

the  intestinal  tract.  In  a  dog  that  had  hungered  eleven 
days,  a  period  of  three  hours  of  exercise  sufficed  to  per- 
mit the  free  passage  of  microorganisms.  It  appears  that 
neither  of  these  factors  is  capable  of  giving  rise  to  this 
degree  of  permeability  when  operating  separately.  Indi- 
vidual peculiarities  were,  however,  observed  in  respect 
to  the  permeability  of  the  tract,  and  these  must  have 
their  explanation  in  special  conditions  in  the  intestine. 

Ficker  does  not  maintain  that  a  full  understanding 
of  the  conditions  favoring  the  permeability  of  the 
intestinal  tract  has  been  reached  through  his  experi- 
ments. He  holds  very  definitely  that  in  fully  grown 
dogs,  in  which  the  intestinal  tract  is  ordinarily  little 
permeable,  it  is  possible  through  inanition  or  fatigue 
or  a  combination  of  the  two,  to  facilitate  a  penetration 
of  the  intestinal  mucous  membrane  which  is  analogous 
to  that  observed  in  the  infantile  tract  and  further  re- 
sembles the  conditions  present  in  the  dying  organism. 
Ficker  suggests  that  under  the  influence  of  powerful 
bodily  action  the  volume  of  the  gastric  juice  and  of 
other  digestive  juices  is  greatly  reduced  and  that  peri- 
stalsis is  diminished,  while  on  the  other  hand  the  lymph 
and  blood  flow  are  actively  accelerated,  all  these  being 
factors  which  might  favor  the  penetration  of  bacteria. 
He  suggests  that  perhaps  the  increased  leucocytosis 
induced  by  active  muscular  exertion  is  responsible  for 
the  increased  extravascular  bactericidal  power  of  the 
serum  which  he  observed,  and  thus  that  the  leucocytes 
can  be  regarded  as  carriers  of  bacteria  from  the  intestinal 
tract.  Such  a  transportation  of  bacteria  by  leucocytes 


INFECTIONS  OF  THE  DIGESTIVE  TRACT        97 

would  presumably  be  facilitated  in  a  high  degree  by  the 
accelerated  movement  of  the  blood  serum  during  active 
exercise.  Ficker  thinks  it  probable,  also,  that  at  the 
time  of  greatly  increased  muscular  exercise  the  body 
cells  generally,  including  those  of  the  intestinal  tract, 
suffer  a  temporary  check  in  their  metabolism  and  hi 
their  ability  to  liberate  energy.  This  temporary  cell 
infirmity  is  supposed  in  some  way  to  influence  the  intes- 
tinal epithelium  so  as  to  favor  the  passage  of  bacteria. 
Ficker  further  suggests  that  through  his  experiments 
are  explained  the  well-known  observations  that  the 
flesh  of  animals  that  have  been  slaughtered  after  having 
been  driven  long  distances  very  quickly  decomposes 
after  the  killing,  while,  on  the  other  hand,  the  flesh  is 
much  better  preserved  in  animals  that  are  allowed  to 
rest  for  several  days  before  being  killed.  He  also  raises 
the  question  whether  the  penetration  of  the  intestinal 
tract  by  bacteria  may  not  explain  some  of  the  phenomena 
that  have  been  noted  after  great  fatigue,  for  example, 
the  so-called  "fever  of  exhaustion,"  and  also  the  state 
designated  by  the  older  physicians  as  "autotyphization." 

PHYLOGENETIC  SIGNIFICANCE   OF  THE  LARGE  INTESTINE 

In  the  study  of  the  physiology  and  pathology  of 
the  digestive  tract  it  is  necessary  to  realize  the  impor- 
tance of  certain  functions  in  the  development  of  the  race 
which  may  be  too  readily  overlooked  because  they  no 
longer  possess  the  significance  for  the  maintenance  of 
life  that  was  formerly  the  case.  There  can  be  little 
doubt  that  one  important  function  of  the  large  intestine 


98        INFECTIONS  OF  THE  DIGESTIVE  TRACT 

is  connected  with  the  inspissation  of  the  contents  of  this 
part  of  the  tract.  In  some  lower  animals  and  in  some 
human  individuals  the  desiccation  of  intestinal  contents 
reaches  so  high  a  grade  that  the  fseces  voided  contain 
only  a  very  low  per  cent,  of  water.  By  means  of  this 
absorption  of  moisture  the  organism  is  protected  against 
a  loss  of  water  which  under  certain  conditions  might 
prove  a  detrimental  condition  in  the  struggle  for  existence. 
It  is  easily  conceivable  that  under  primitive  conditions 
of  life,  where  water  is  not  always  readily  obtainable, 
those  animals  which  were  best  able  to  conserve  their 
water  and  salts  would  have  a  material  advantage  over 
animals  less  well  able  to  prevent  this  waste.  In  many 
mammals  urine  of  very  low  specific  gravity  is  excreted, 
although  in  the  glomeruli  of  the  kidneys  in  these  same 
animals  the  concentration  of  the  urine  is  extremely 
high.  If  it  were  not  for  the  powerful  resorptive  action 
of  the  epithelia  of  the  convoluted  and  other  tubules  of 
the  kidney,  the  organism  would  be  subjected  to  an 
enormous  loss  of  water.  Under  conditions  where 
water  is  freely  obtainable  such  a  loss  would,  perhaps, 
have  little  significance,  bu,t  where  the  water  supply  is 
uncertain  such  wastefulness  on  the  part  of  the  organism 
would  soon  lead  to  death.  Thus  in  the  large  intestine  as 
well  as  in  the  tubules  of  the  kidney  we  have  to  recognize 
mechanisms  protective  to  the  life  of  the  individual 
through  provision  against  the  waste  of  water.  In  the  case 
of  man  this  function  is  of  relatively  little  significance 
at  the  present  time  since  water  may  usually  be  obtained 
in  abundance.  It  seems  probable  that  in  addition  to  the 


INFECTIONS  OF  THE  DIGESTIVE  TRACT        99 

function  just  mentioned  the  large  intestine  has  often 
served  as  a  reservoir  for  food,  but  this  function  certainly 
is  superfluous  in  man.  These  considerations  are  of 
importance ;  for  if  it  can  be  shown  that  the  large  intestine 
is  not  needed  either  for  purposes  of  inspissation  or  as  a 
reservoir  or  as  a  place  of  importance  in  carrying  certain 
digestive  processes  to  an  end,  there  is  no  reason  why  the 
intestine  should  not,  under  certain  conditions  of  disease, 
be  shortened  by  the  elimination  of  a  large  part  of  the 
colon.  There  is  some  difference  of  opinion  as  to  whether 
animals  can  live  without  the  large  intestine,  but  the  bal- 
ance of  evidence  is  in  favor  of  their  being  able  to  main- 
tain life  even  after  the  large  intestine  has  been  excluded. 
There  are  also  instances  in  human  beings  that  point  to 
the  same  conclusion.  Dr.  Bryant  of  New  York  tells 
me  that  in  one  instance  he  practiced  the  insertion  of  the 
ileum  into  the  rectum.  The  patient  was  a  woman  who 
lived  a  considerable  period  of  time  in  this  condition 
without  suffering  in  nutrition. 

THE  IMPORTANCE  OF  PROMPT  RESORPTION  FROM  THE 
SMALL  INTESTINE 

It  is  almost  self-evident  that  the  prompt  resorption  of 
food  from  the  small  intestine  is  one  of  the  most  impor- 
tant factors  in  preventing  the  occurrence  of  excessive 
putrefactive  conditions  in  the  digestive  tract.  The  pas- 
sage of  large  quantities  of  partially  digested  proteid 
material  into  the  region  of  the  intestine  where  anaerobic 
conditions  prevail  must  necessarily  greatly  facilitate  the 
bacterial  decomposition  of  proteids  in  the  digestive  tract. 


100      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

As  will  be  pointed  out  in  dealing  with  the  methods  of 
diminishing  chronic  excessive  intestinal  putrefaction, 
those  measures  which  are  designed  to  secure  prompt 
digestion  and  prompt  absorption  from  the  small  intestine 
are  of  the  greatest  significance  in  limiting  bacterial  de- 
compositions* 

The  administration  of  a  cathartic  which  acts  imper- 
fectly (that  is,  which  carries  partly  digested  food  from 
the  small  intestine  into  the  colon  without,  however, 
securing  an  evacuation)  leads  to  conditions  similar  to 
those  following  an  excessive  meal.  In  some  persons 
this  miscarriage  of  a  cathartic  is  followed  by  headache 
and  flatulence,  in  others  by  more  serious  signs  of  intoxi- 
cation such  as  weakness  in  the  muscles.  In  normal 
persons  these  effects  are  relatively  slight;  in  persons 
whose  digestive  tracts  are  the  seat  of  infection  with 
putrefactive  anaerobes  the  evidence  of  excessive  fer- 
mentation and  putrefaction  is  much  more  pronounced. 

THE   PHENOMENON   OF   SUBSTITUTION 

I  am  convinced  that  what  may  be  termed  the  phenom- 
enon of  substitution  of  flora  in  the  digestive  tract  is  a 
common  and  significant  occurrence  in  the  course  of  many 
derangements  of  the  digestive  tract.  By  substitution  is 
meant  the  temporary  replacement  of  one  type  of  micro- 
organism normally  abundantly  present  in  the  digestive 
tract  by  an  allied  form  which,  though  perhaps  normally 
present  in  small  numbers,  never  assumes  a  dominant  place 
during  health.  The  substitution  may  be  complete  or  in- 
complete and  may  be  a  temporary  or  a  prolonged  phe- 


INFECTIONS  OF  THE  DIGESTIVE  TRACfr      101 

nomenon.  After  a  time  the  substituting  microorganism 
loses  its  prominent  place  and  in  its  stead  the  obligate 
bacteria  of  the  tract  again  become  dominant. 

The  phenomenon  of  substitution  is  one  that  most 
frequently  involves  temporary  replacements  of  the  colon 
bacilli  in  the  lower  part  of  the  large  intestine  and  also  in 
higher  portions.  An  example  of  what  is  meant  by  such 
substitution  is  afforded  by  the  folio  whig  case.  A  woman 
of  twenty-five  years  of  age  developed  measles  and  soon 
after  convalescence  became  ill  with  what  was  apparently 
a  condition  of  mucous  colitis,  lasting  about  one  month 
and  attended  by  slight  fever.  Studies  of  the  flora  made 
toward  the  end  of  the  period  of  mucous  colitis  showed 
that  the  faecal  fields  contained  an  excessive  number  of 
diplococci,  and  the  sediments  of  the  fermentation  tubes 
exhibited  streptococcal  growths  in  great  abundance. 
On  litmus  gelatin  plates  made  from  faecal  suspensions 
it  was  found  that  the  dominant  organism  resembled 
colon  bacilli  in  appearance,  but  differed  from  them  in 
forming  acid  very  slowly.  Many  colonies  were  fished 
from  these  plates  and  studied,  but  none  were  found  which 
could  be  called  colon  bacilli.  The  organisms  obtained 
differed  from  colon  bacilli  in  making  no  indol  and  in 
possessing  only  feeble  powers  of  gas  production  and  of 
acid  formation  on  glucose.  They  irregularly  fermented 
levulose  and  lactose.  They  coagulated  milk  only  after 
a  lapse  of  ten  days,  and  then  the  coagulation  was  in- 
complete. They  were  actively  motile  Gram-negative 
bacteria.  Two  weeks  later,  during  the  progress  of  con- 
valescence from  the  condition  of  mucous  colitis,  it  was 


102      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

found  that  the  fsecal  suspensions  gave  on  the  gelatin 
plates  large  numbers  of  bacteria  of  the  type  just  men- 
tioned and  in  addition  contained  considerable  numbers 
of  true  colon  bacilli.  One  month  after  the  first  exami- 
nation the  fsecal  suspensions  showed  the  presence  of 
large  numbers  of  colon  bacilli,  which  had  now  become  the 
dominant  type.  From  the  litmus  gelatin  plates  a  very 
small  proportion  of  bacteria  were  isolated  which  were 
incapable  of  coagulating  milk,  made  no  indol,  and  had 
little  effect^jifLQn  the  sugars.  It  was  evident  that  the 
substituted  bacteria  were  now  in  a  small  minority. 
The  substituted  microorganisms  in  this  case  resembled 
the  bacilli  of  typhoid  fever  except  in  the  fact  that  they 
were  able  to  ferment  glucose  and  possessed  the  ability 
to  ferment  lactose  and  levulose  in  an  irregular  manner. 
I  have  in  several  instances  met  with  cases  of  substi- 
tution in  which  the  colon  bacilli  have  disappeared  from 
the  stools  and  have  been  replaced  temporarily  or  per- 
manently by  other  types  of  bacteria.  Dysentry  bacilli 
may  temporarily  replace  obligate  colon  bacilli. 

THE   PRESENCE    OF    PATHOGENIC    BACTERIA    IN   THE 
DIGESTIVE   TRACT   IN   HEALTH 

Evidence  is  gradually  accumulating  which  goes  to 
show  that  pathogenic  microorganisms  may  be  present 
in  moderate  or  even  considerable  numbers  in  the  intes- 
tinal tract  under  some  conditions  without  giving  rise 
to  clinical  manifestations  of  deranged  function.  It  is 
now  well  known  that  moderate  numbers  of  typhoid 
bacilli  may  in  some  instances  be  found  in  the  stools 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      103 

of  patients  who  have  lately  had  typhoid  fever. 
Here  the  explanation  of  the  absence  of  symptoms  is 
doubtless  to  be  sought  in  local  or  local  and  general  con- 
ditions of  immunity.  There  appear,  however,  to  be 
instances  in  which  there  is  no  evidence  that  typhoid 
fever  has  occurred  but  in  which  nevertheless  moderate 
numbers  of  organisms  may  be  obtained  from  the  fseces. 
The  same  facts  hold  true  for  the  bacilli  of  dysentery. 
Duval  has  shown  that  dysentery  bacilli  are  present 
occasionally  in  small  numbers  in  the  stools  of  normal 
individuals,  and  this  observation  has  been  confirmed  by 
others.1  We  have  noted  the  presence  of  B.  pyocyaneus 
occasionally  in  the  digestive  tract  of  persons  apparently 
in  the  best  of  health.  It  is  likely,  however,  that  in  all 
these  cases  the  pathogenic  organisms  in  question  are 
held  in  check  by  the  bacteria  present  in  the  digestive 
tract  or  by  the  bacteria  and  the  intestinal  secretions  so 
that  they  are  unable  to  multiply  in  a  significant  manner 
or  to  gain  entry  into  the  cells  of  the  mucous  membrane. 
It  seems  not  unreasonable  to  suppose  that  errors  in  diet 
or  depressed  general  conditions  favor  the  multiplication 
and  penetration  of  pathogenic  bacteria  that  have  for 
some  time  been  present  in  a  slumbering  state.  Irritant 
foods  may  possibly  so  alter  the  secretions  of  the  digestive 
tract  as  to  favor  definite  infection  by  the  semi-parasitic 
bacteria  that  are  present. 
The  considerations  just  mentioned  as  applying  to  the 

1  In  some  of  the  apparently  normal  children  from  whom  Dr. 
Wollstein  obtained  dysentery  bacilli  there  were  subsequently 
developed  the  clinical  indications  of  dysentery. 


104      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

bacilli  of  typhoid  fever,  of  dysentery,  and  of  B.  pyocyaneus 
probably  hold  equally  true  of  the  more  saprophytic  forms, 
such  as  the  microorganisms  concerned  in  chronic  exces- 
sive intestinal  putrefaction.  It  is  certain  that  the  intes- 
tine may  harbor  considerable  numbers  of  B.  putrificus 
and  B.  aerogenes  capsulatus  or  both  of  these  together 
without  the  development  of  clinical  manifestations.  A 
variety  of  conditions  may  be  presumed  to  so  favor  the 
development  of  these  anaerobes  that  their  products, 
instead  of  being  formed  in  such  small  amounts  as  to 
be  harmless,  begin  to  exert  a  detrimental  effect  upon 
the  organism.  Especially  important  in  this  connection 
are  influences  which  alter  the  character  of  the  secretions 
in  the  large  intestine  or  bring  into  the  large  intestine 
unusually  large  quantities  of  partly  digested  proteid  food. 
There  is  an  important  practical  aspect  to  the  fact 
that  pathogenic  organisms  inhabit  the  intestinal  tract 
without  giving  obvious  clinical  signs  of  their  presence. 
A  good  quality  of  milk  or  meat,  free  from  pathogenic 
bacteria,  may  be  blamed  for  bacterial  decompositions  of 
a  harmful  kind  which  are  in  reality  due  to  abnormal  bac- 
terial conditions  prevailing  in  the  digestive  tract  before 
the  use  of  the  food  under  suspicion.  In  certain  con- 
ditions of  the  digestive  tract  an  excessive  or  even  a 
moderate  meal  of  proteid  food  will  precipitate  an  intoxi- 
cation or  a  seizure  of  vomiting  or  diarrhoea.  There 
are  cases  classed  as  "ptomaine  poisoning"  in  which  the 
digestive  tract,  rather  than  the  food,  is  responsible  for 
the  observed  disorders. 


CRITERIA  EMPLOYED  IN  THE  CLASSIFICATION 
OF  BACTERIA  OF  THE  GASTRO-ENTERIC 
TRACT 

IT  appears  not  out  of  place  to  refer  briefly  to  the  cri- 
teria employed  in  classifying  the  bacteria  of  the  gastro- 
enteric  tract  although  these  standards  of  judgment  do 
not  differ  from  those  of  bacteria  generally.  The  cul- 
tural characters  of  the  growths  upon  ordinary  media 
must  be  regarded  as  relatively  less  important  in  form- 
ing a  judgment  as  to  the  character  of  given  organisms 
than  was  formerly  the  case,  since  in  the  early  days  of 
bacteriology  such  cultural  characters  constituted  our 
chief  reliance  in  identification.  While  the  cultural  char- 
acters of  a  microorganism  derived  from  the  digestive 
tract  must  in  every  instance  be  taken  into  account, 
these  do  not  usually  suffice  to  give  more  than  a  suspicion 
of  the  identity  of  the  bacterium  in  question.  In  general 
it  may  be  said  that  the  cultural  characters  do  not  pos- 
sess a  high  grade  of  permanence  and  are,  moreover,  often 
not  specific  within  certain  groups.  For  example,  within 
the  group  of  colon  bacilli  one  finds  many  organisms  which 
must  be  regarded  as  distinct  but  which  nevertheless  give 
practically  undistinguishable  growths  on  the  ordinary 
culture  media.  Indeed,  a  strain  of  colon  bacillus  may  in 
time  come  to  vary  quite  widely  from  its  original  appear- 
ance upon  a  given  medium.  The  cultural  characters  of 
microorganisms  are  often  much  influenced  by  physical 

105 


106      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

conditions  pertaining  to  a  culture  medium.  For  example, 
Dunham  obtained  widely  different  appearances  in  growths 
of  the  same  typhoid  bacillus  when  grown  in  gelatin 
plates  in  which  the  gelatin  possessed  varying  degrees  of 
concentration  and  slightly  different  chemical  characters. 
The  morphological  characters  of  organisms  are  cer- 
tainly important  to  consider  and  must  be  known  as 
a  matter  of  course  in  any  study  of  bacteria,  but  within 
groups  of  closely  related  organisms  morphology  itself 
gives  us  little  aid.  The  question  of  motility  is  one  of  a 
good  deal  of  importance  and  should  always  be  considered. 
In  general  within  a  group  of  colon-like  organisms  a  high 
grade  of  motility  suggests  pathogenicity,  but  the  absence 
of  motility  or  a  low  grade  of  it  does  not  point  in  the 
opposite  direction,  since  pathogenic  types  of  bacilli  in 
the  dysentery  group  presumably  not  distantly  related 
to  the  colon  bacilli  are  non-motile.  The  determination 
of  the  staining  characters  of  the  organism  with  the  Gram 
method  is  most  helpful  provided  a  uniform  method  of 
procedure  be  employed.  In  the  absence  of  a  uniform 
technique  the  Gram  method  is  less  good  than  a  simple 
stain,  since  it  serves  only  to  confuse.  Of  great  impor- 
tance for  the  classification  of  the  bacteria  of  the  gastro- 
enteric  tract,  as  of  bacteria  generally,  are  the  biochemical 
properties.  These  biochemical  characters  include  the 
cleavage  abilities  of  the  organism  with  special  reference 
to  their  action  on  the  soluble  carbohydrates1  with  the 
production  of  acid  and  gas,  their  ability  to  produce  indol 

1  The  great  importance  of  this  method  of  studying  bacteria 
was  first  pointed  out  by  Professor  Theobald  Smith  in  connection 
with  the  differentiation  of  typhoid  and  colon  bacilli. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      107 

and  skatol,  and  to  liberate  sulphur  products  such  as 
hydrogen  sulphide  and  methyl  mercaptan.  The  high 
grade  of  permanence  of  the  fermentative  characters  of 
bacteria  give  this  test  much  value.  This  permanence 
is  probably  more  marked  within  certain  groups  such  as 
the  colon-typhoid  group  than  in  certain  others,  as,  for 
example,  the  group  of  streptococci.  Strains  of  colon 
bacilli  may  be  carried  through  a  long  series  of  sugar- 
bouillon  fermentation  tubes  without  appreciably  modify- 
ing in  a  quantitative  way  their  ability  to  form  gas  and 
acid.  In  a  series  of  experiments  in  this  direction  which 
was  carried  out  by  Mr.  H.  C.  Ward,  it  was  found  that 
strains  of  colon  bacilli  which  had  grown  for  a  long  time 
upon  a  succession  of  sugar-bouillon  tubes  grew  less  well 
upon  peptone  bouillon  than  had  previously  been  the  case. 
On  being  cultivated  in  peptone  bouillon  after  a  long 
period  of  growth  on  sugar  bouillon  it  was  found  that  they 
produced  only  about  one-half  as  much  indol  as  had  pre- 
viously been  the  case .  This  result  might  easily  have  been 
interpreted  as  an  evidence  that  the  organisms  in  question 
were  losing  their  ability  to  make  indol  upon  peptone 
bouillon.  Careful  examinations  of  the  growths,  however, 
showed  that  the  diminished  production  of  indol  was 
to  be  referred  rather  to  an  impaired  ability  of  the  colon 
bacilli  to  grow  upon  peptone  bouillon,  than  to  a  real 
inability  to  make  indol.  The  formation  of  indol  is  a 
character  of  considerable  importance  in  the  classification 
of  bacteria,  but  there  is  some  evidence  that  it  is  not  so 
permanent  and  invariable  a  characteristic  as  the  ability 
of  the  bacteria  to  ferment  certain  sugars.  Much  more 


108      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

work  is  required  to  establish  the  exact  position  of  indol 
production  as  a  criterion  for  the  classification  of  bacteria. 
Unfortunately,  nearly  all  that  we  know  at  the  present 
time  about  the  production  of  indol  is  based  upon  the 
nitroso-indol  test,  which  possesses  two  grave  disadvan- 
tages. First,  this  test  is  not  highly  sensitive  in  the  detec- 
tion of  indol,  and  secondly,  the  test  as  usually  practiced 
does  not  exclude  the  possibility  of  the  presence  of  other 
substances  which  react  with  indol.  I  consider  it  desir- 
able to  replace  the  old  nitroso-indol  test  by  the  dimeth- 
ylamidobenzaldehyde  reaction  first  described  by  Pro- 
fessor Ehrlich  and  which  is  much  more  delicate  than 
the  nitroso-indol  test.  For  quantitative  determinations 
of  indol  the  yS-naphthaquinone-sodium-monosulphonate 
method  which  I  have  described  is  unquestionably  the 
best.  There  is  little  doubt  that  in  the  classification  of 
the  intestinal  bacteria  more  and  more  stress  will  be  laid 
on  the  biochemical  characters  of  the  organisms  in  ques- 
tion. The  pathogenicity  of  an  organism  is,  of  course,  a 
highly  important  character,  but  is  far  more  variable  in 
general  than  the  biochemical  characters  just  mentioned. 
Virulent  bacteria  may  easily  lose  their  virulence  or  have 
it  greatly  increased,  according  to  the  circumstances  under 
which  they  grow.  The  character  of  the  conditions  under 
which  an  organism  has  been  cultivated  must,  therefore, 
be  carefully  borne  in  mind  in  drawing  conclusions  as  to 
this  point.  An  organism  which  has  long  been  grown  in 
the  laboratory  may  easily  lose  its  virulence  on  ordinary 
media.  On  the  other  hand,  some  microorganisms, 
such  as  diphtheria  bacilli,  may  be  grown  for  years  on 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      109 

artificial  culture  media  of  the  same  composition  and  still 
remain  strikingly  constant  with  respect  to  the  activity  of 
the  toxins  produced.  The  aerobic  or  anaerobic  charac- 
ters of  microorganisms  are  of  great  importance  in  the 
classification  of  intestinal  bacteria,  since  the  putrefactive 
processes  in  the  digestive  tract  are  carried  on  largely 
through  the  agency  of  strict  anaerobes.  No  study  of  the 
bacteria  of  the  gastro-enteric  tract  can  be  considered 
thorough  which  does  not  take  the  strict  anaerobes  into 
account.  This,  of  course,  involves  the  use  of  anaerobic 
technique.  Some  highly  aerobic  bacteria,  like  the  micro- 
organisms of  cholera  and  the  bacilli  of  tuberculosis, 
multiply  very  poorly  under  strictly  anaerobic  conditions. 
The  majority  of  pathogenic  microorganisms  in  man  are, 
however,  facultative  anaerobes  capable  of  growing  under 
anaerobic  as  well  as  aerobic  conditions,  although  the  anae- 
robic growth  may  be  much  less  active  than  the  develop- 
ment in  the  presence  of  air.  The  ability  of  organisms  to 
make  spores  is  another  feature  which  has  to  be  taken  into 
consideration  in  any  classification  of  bacteria.  Most  of 
the  strict  anaerobes  of  the  intestinal  tract  —  possibly 
all  of  them  —  are  capable  of  sporulating  under  certain 
conditions,  and  this  is  a  feature  of  great  significance  for 
their  persistence  in  the  gastro-enteric  tract,  since  in  the 
absence  of  the  ability  to  sporulate  in  the  tract  the  vege- 
tative forms  might  easily  lose  their  hold  and  die  out.  Of 
late  years  much  attention  has  been  given  to  the  aggluti- 
native properties  of  bacteria  growing  in  the  intestinal 
tract,  with  results  of  great  importance  for  the  classifica- 
tion of  these  bacteria.  It  was  at  first  supposed  that  the 


110      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

agglutinative  characters  of  certain  intestinal  bacteria 
such  as  typhoid  and  dysentery  organisms  with  human 
or  experimentally  induced  sera  possess  a  high  degree  of 
specificity.  There  was  also  at  first  an  inclination  to 
believe  that  two  bacteria  of  different  origin  possessing 
the  same  agglutinative  characters  with  one  serum  were 
brought  very  close  together  by  virtue  of  this  fact.  It  is 
now  clear  that  the  failure  to  distinguish  between  group 
or  common  agglutinins  and  specific  agglutinins  may  lead 
one  to  think  bacteria  are  identical  when  this  is  really  not 
so.  The  group  agglutinins  may  to  a  considerable  extent 
be  removed  by  the  procedure  of  absorption  which  has 
lately  come  into  use.  By  means  of  absorption  methods 
it  becomes  possible  to  largely  remove  the  common 
agglutinins  from  a  serum  which  contains  them  by  bring- 
ing this  serum  into  contact  with  bouillon  cultures  of  the 
bacteria  in  question  and  after  a  certain  period  of  contact 
filtering  off  the  bacteria,  which  have  absorbed  from  the 
serum  a  large  part  of  the  common  agglutinins.  The 
specific  agglutinative  properties  of  the  serum  now  come 
very  clearly  into  play  and  may  be  a  great  aid  in  deter- 
mining the  relationship  of  two  microorganisms  suspected 
of  standing  in  close'  relation  to  each  other.  The  value 
of  this  absorption  test  is  somewhat  in  question  in  some 
laboratories,  but  it  has  given  a  high  degree  of  satisfaction 
in  the  laboratory  of  the  Board  of  Health  in  New  York 
City,  where  it  has  been  employed  extensively  and  sys- 
tematically by  Dr.  Park  and  Dr.  Collins.1 

1  The  absorption  method  has  also  been  successfully  employed 
by  Dr.  E.  K.  Dunham  in  his  careful  study  of  the  agglutinins  of  the 
meningococcus. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      111 

The  agglutinative  characters  of  many  pathogenic  bac- 
teria are  remarkably  fixed  properties.  Dr.  Theobald 
Smith  attempted  to  induce  variations  in  the  agglutina- 
tive characters  of  hog-cholera  bacilli  and  colon  bacilli 
by  treating  a  series  of  sensitive  experimental  animals 
with  the  bacteria  to  be  tested.  He  met  with  no  success. 
Dr.  Smith  tells  me,  however,  that  he  thinks  the  chances 
for  success  in  modifying  the  agglutinative  characters  of 
the  bacteria  would  have  been  greater  had  he  tried  more 
resistent  animals  than  were  used,  since  this  would  have 
afforded  more  opportunity  to  excite  antagonism  on  the 
part  of  the  microorganisms,  and  with  this,  some  altera- 
tion in  agglutinative  properties.  It  is  stated  that  the 
agglutinative  characters  of  some  streptococci  are  more 
subject  to  variation  than  those  of  the  B.  coli  group. 

METHODS   OF   INVESTIGATION 

It  is  desirable  to  speak  briefly  here  of  the  methods 
that  have  been  employed  in  some  of  the  investigations 
with  which  this  volume  deals.  Some  of  these  methods 
are  well  known,  others  are  new.  They  relate  in  part 
to  the  study  of  the  morphological  and  cultural  charac- 
ters of  the  bacterial  organisms  found  in  the  digestive 
tract  under  different  conditions,  but  they  have  to  do 
mainly  with  the  products  of  the  life  activities  of  these 
bacteria  upon  different  nutrient  media. 

Character  of  the  Microscopical  Fields.  —  By  far  the 
most  helpful  method  of  studying  the  microscopical 
fields  is  with  the  aid  of  the  Gram  stain.  The  routine 


112      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

examination  of  the  intestinal  contents  by  means  of  this 
stain  is  a  real  aid  in  forming  a  judgment  as  regards  the 
presence  or  absence  of  certain  types  of  bacteria  in  the 
digestive  tract.1  There  are  many  conditions  in  which, 
as  must  be  obvious,  it  can  be  of  little  service.  There 
are  instances  in  which  Gram-stained  microscopical  fields 
appear  entirely  normal,  but  after  cultural  and  chemical 
studies  it  is  evident  that  abnormal  decompositions  are 
at  work  and  that  pathological  microorganisms  are  pres- 
ent. On  the  other  hand,  one  may  often  form  an  opin- 
ion from  the  mere  study  of  the  fields  as  to  whether  the 
bacteria  present  are  capable  of  initiating  putrefactive 
processes  or  not.  In  order  to  make  the  staining  of  any 
value  it  is  necessary  that  the  method  should  be  carried 
out  in  a  uniform  manner.  The  suspension  of  the  flora 
used  should  not  be  too  concentrated,  as  the  pictures  may 
be  confused  through  an  excessive  number  of  bacteria. 
Suspensions  of  fsecal  material  in  the  proportion  of  one 

1  In  studying  the  bacteriology  of  the  intestinal  tract  it  is  greatly 
to  be  desired  that  very  fresh  specimens  of  the  intestinal  contents 
be  employed,  since  it  may  happen  that  certain  delicate  forms  of 
organisms  may  otherwise  quickly  die.  In  the  case  of  colon  bacilli, 
of  many  coccal  forms,  and  of  most  of  the  anaerobes  a  period  of  delay 
appears  to  make  little  difference.  In  some  of  our  investigations 
we  have  worked  with  strictly  fresh  material,  but  it  has  necessarily 
often  happened  that  there  was  a  delay  of  a  few  hours  and  some- 
times of  even  greater  time  before  cultures  were  made.  The  danger 
in  these  cases  is  simply  the  danger  of  losing  some  types  which 
might  otherwise  be  represented  in  the  plates  and  fermentation 
tubes.  It  is  stated  by  some  writers  that  B.  bifidus  is  sensitive  to 
a  depression  of  temperature,  but  we  have  not  always  found  this 
to  be  the  case  with  the  temperature  of  the  ice  box,  since  we  have 
been  able  to  obtain  growths  of  that  organism  in  sugar  bouillon 
even  after  several  days'  residence  of  the  material  upon  ice. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      113 

part  by  weight  to  ten  parts  of  normal  salt  solution  answer 
very  well  as  a  material  for  making  the  smears.  The 
following  technique  serves  satisfactorily  for  routine  work. 
One  stains  for  three  minutes  with  the  Gram  solution 
of  gentian  violet.  The  solution  is  then  allowed  to  run 
off  the  slide,  but  the  latter  is  not  washed.  Lugol's  solu- 
tion of  iodine  is  then  permitted  to  act  for  two  minutes. 
The  slide  is  now  rinsed  with  water  and  decolorization 
is  practiced  for  one-half  minute  by  means  of  absolute 
alcohol.  The  smear  is  then  restained  with  a  fuchsin 
solution.  Unless  one  employs  approximately  the  same 
technique,  varying  and  confusing  results  are  obtained 
which  make  it  almost  impossible  to  say  with  confidence 
which  organisms  are  Gram-negative  and  which  are  Gram- 
positive. 

From  the  use  of  the  Gram  method  one  obtains  some 
idea  as  to  the  numbers  of  microorganisms  resembling 
the  colon  bacilli  in  morphology;  one  may  form  a  judg- 
ment as  to  the  state  of  their  preservation,  as  to  the  pres- 
ence or  absence  of  slender,  long,  Gram-negative  organ- 
isms of  the  type  of  B.  liquefaciens  ilei;  a  judgment  may 
be  formed  as  to  the  numbers  of  Gram-positive  diplococci 
and  other  coccal  forms ;  an  opinion  may  be  formed  as  to 
the  probability  of  the  presence  of  B.  bifidus,  especially 
in  its  unbranched  form;  and  finally  it  is  possible,  after 
one  has  had  experience,  to  make  an  estimate  as  to  whether 
free  spores  and  spore-holding  organisms  and  vegetative 
anaerobic  forms  are  present  in  excessive  numbers.  None 
of  these  microscopical  appearances  can  be  regarded  as 
positive  evidence  of  the  identity  of  the  dominant  bacteria 


114      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

present  until  this  has  been  determined  by  cultural 
methods.  It  may,  however,  aid  one  in  forming  conclu- 
sions that  are  valuable  on  account  of  their  high  degree 
of  probability.  In  the  case  of  a  given  individual,  iso- 
lation by  careful  plating  and  identification  by  suitable 
methods  of  any  dominant  organism  becomes  a  great  aid 
to  subsequent  interpretation  of  the  Gram-stained  field, 
even  though  one  may  not  have  the  opportunity  to  make 
further  isolations  and  identification  in  the  same  patient. 
There  are  many  applications  of  the  Gram  stain  that 
may  advantageously  be  made  in  the  study  of  intestinal 
disorders,  quite  aside  from  the  direct  study  of  the  faeces 
and  intestinal  material  obtained  through  the  use  of 
cathartics.  A  study  of  the  types  of  bacteria  that  are 
dominant  at  different  levels  of  the  intestinal  tract  in 
persons  dying  of  various  diseases  is  greatly  facilitated  by 
the  use  of  Gram  staining.  This  method  of  study  of  the 
bacteria  at  different  levels  has  not  yet  received  the  at- 
tention it  deserves.  I  consider  it  especially  important 
to  determine  the  distribution  of  the  anaerobes  in  the 
small  intestine  in  numbers  sufficiently  great  to  enable 
them  to  put  their  stamp  on  the  character  of  the  intestinal 
decomposition.  The  Gram  stain  further  has  proved 
highly  useful  in  the  study  of  the  sediments  in  all  the 
fermentation  tubes  inoculated  with  the  mixed  faBcal 
flora.  Moreover,  the  same  method  has  given  consider- 
able information  in  the  study  of  the  sediments  obtained 
in  various  media  on  which  certain  mixed  flora  have  been 
grown  from  seven  to  ten  days.  It  is  sometimes  desira- 
ble to  make  use  of  a  staining  method  for  spores  in  order 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      115 

to  obtain  an  idea  of  the  numbers  of  free  spores  present. 
Without  this  procedure  one  is  apt  to  underestimate  their 
number.  The  faecal  flora  may  also  be  stained  directly 
for  capsules  by  Welch's  acetic  acid  method. 

I  shall  not  attempt  here  to  discuss  fully  methods  of 
isolation  and  identification  of  individual  bacteria.  The 
methods  generally  in  use  for  making  plate  cultures  are 
those  which  have  been  employed.  In  the  case  of  the 
bacilli  of  typhoid  fever,  dysentery,  and  allied  organisms 
this  subject  has  already  been  fully  developed  by  highly 
trained  workers.  The  study  of  the  diplococci  and  other 
coccal  forms  is  one  that  has  been  relatively  neglected 
(except  in  the  case  of  acute  infections)  and  is  deserving 
of  much  fuller  development.  On  the  subject  of  the  anae- 
robes of  the  large  intestine  almost  nothing  has  been  done, 
partly,  perhaps,  on  account  of  the  difficulties  of  anae- 
robic technique.  Some  acute  infections  with  anaerobes 
have  indeed  been  studied,  notably  by  Tissier  and  by 
Klein,  but  until  recently  the  chronic  processes  dependent 
on  excessive  development  of  putrefactive  anaerobes  have 
escaped  attention.  The  necessity  of  furnishing  anaerobic 
conditions  for  the  growth  of  some  of  these  bacteria  con- 
siderably increases  the  difficulties  of  identification,  but 
they  are  by  no  means  insuperable.  Where  a  high  degree 
of  anaerobiosis  has  been  desired,  we  have  found  it  help- 
ful to  make  use  of  a  stream  of  compressed  hydrogen 
instead  of  using  hydrogen  generated  in  the  laboratory. 
This  is  followed  by  the  employment  of  the  pyrogallic 
method  for  removing  the  last  trace  of  oxygen.  Where 
a  somewhat  less  high  degree  of  anaerobiosis  suffices  it 


116      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

is  very  convenient  to  make  use  of  the  simple  method, 
recently  described  by  Hans  Zinsser  1  from  the  Depart- 
ment of  Pathology  in  Columbia  University.  Here  two 
crystallizing  dishes  are  made  to  do  service  for  obtaining 
anaerobic  growths .  The  smaller  dish  containing  the  inoc- 
ulated agar  is  inverted  inside  the  larger  dish,  the  oxygen 
being  exhausted  by  the  pyrogallic  method.  Water,  on 
the  surface  of  which  oil  is  placed,  serves  as  a  seal.  This 
method  should  serve  to  remove  some  of  the  obstacles  to 
the  study  of  anaerobes. 

The  identification  of  the  anaerobes  calls  for  a  good  deal 
of  patience  and  care.  The  anaerobic  life  of  the  large 
intestine  (especially  in  disease)  having  been  so  little 
studied,  it  is  not  unlikely  that  new  varieties  will  be  found 
which  have  heretofore  escaped  notice.  A  growth  of 
B.  bifidus  and  other  acidophiles  occurs  under  anaerobic 
conditions  in  both  glucose  and  plain  agar,  if  one  takes 
the  precaution  to  make  up  the  media  so  that  they  con- 
tain 0.5  per  cent,  of  acetic  acid.2  In  the  study  of  B. 
aerogenes  capsulatus  it  is  important  to  use  blood  agar  in 
order  to  obtain  the  conditions  proper  for  the  growth 
of  these  bacilli.  The  use  of  one  cubic  centimeter  of 
defibrinated  rabbit's  blood  to  eight  cubic  centimeters  of 
sugar  agar  answers  well. 

In  studying  the  characters  of  the  organisms  for  the 
purpose  of  identification  the  fermentation  tubes  are  ex- 
tremely helpful,  as  first  pointed  out  by  Professor  Theo- 

1 "  A  Simple  Method  for  the  Plating  of  Anaerobic  Organisms," 
Journ.  of  Exper.  Med.,  viii,  p.  542,  1906. 

2  A  beer-wort  medium  may  be  conveniently  used. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      117 

bald  Smith.  Anaerobic  organisms  in  general  grow  much 
better  in  the  closed  limb  of  the  tube  on  sugar  bouillon 
in  the  presence  of  bits  of  sterile  tissue  (such  as  liver  from 
a  guinea-pig  or  rabbit),  and  in  some  cases,  as  in  that  of 
B.  aerogenes  capsulatus,  they  do  not  grow  in  the  ab- 
sence of  this  aid.  The  identification  of  the  anaerobes 
involves  the  study  of  their  cultural  characteristics,  of 
their  ability  to  form  gas  on  sugar  media,  and  the  de- 
termination of  their  gas  formula.  The  estimation  of 
the  ratio  between  the  hydrogen  and  the  carbon  dioxide 
formed  is  an  important  point  in  identification  first 
suggested  by  Theobald  Smith.  It  is  easy  to  determine 
this  point  by  adding  caustic  potash  to  the  contents  of 
the  fermentation  tube,  this  being  followed  by  absorp- 
tion of  the  carbon  dioxide. 

The  influence  of  the  growth  of  anaerobes  upon  milk, 
especially  litmus  milk,  is  easily  studied  in  the  fermenta- 
tion tubes  and  gives  considerable  aid  in  identification. 
For  example,  B.  aerogenes  capsulatus  quickly  makes  acid 
on  milk  and  sets  up  a  stormy  fermentation  due  to  the  very 
rapid  production  of  gas  from  milk-sugar.  It  also  acts 
proteoclastically  on  the  casein,  and  the  coagulated  milk 
is  partly  digested  and  broken  into  small  masses.  This 
behavior  is  in  marked  contrast  to  that  of  the  bacillus 
of  malignant  oedema.  Very  rapid  and  abundant  gas 
production  from  milk  occurs  through  the  agency  of  B. 
cloacce,  an  organism  not  rarely  found  in  the  human 
intestine. 

The  pathogenicity  of  the  isolated  anaerobes  is  also 
a  point  of  importance  in  the  establishment  of  their 


118      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

identity.  There  is  a  considerable  group  of  strict  anaer- 
obes whose  members  are  able  to  induce  in  guinea-pigs 
(when  subcutaneously  injected)  certain  characteristic 
lesions,  including  hsemorrhagic  oedema,  necrosis  of  cells 
due  to  proteoclastic  enzymes,  and  in  certain  cases  evolu- 
tion of  gas.  Finally,  the  introduction  of  cultures  of 
putrefactive  anaerobes  into  the  circulation  of  a  living 
rabbit  which  is  killed  in  the  course  of  a  few  minutes  and 
then  incubated  is  sometimes  a  method  very  helpful  for 
the  establishment  of  the  identity  of  an  anaerobic  micro- 
organism. This  method,  which  was  first  employed  by 
Welch  and  Nuttall,1  must  be  regarded  as  an  extremely 
important  means  of  revealing  not  only  the  gas-forming 
properties  of  a  pure  culture  of  anaerobes,  but  also  of 
showing  those  of  a  suspension  of  the  mixed  fa3cal  flora. 
Here  the  blood  and  tissues  of  the  rabbit  act  as  a  pecul- 
iarly favorable  culture  medium  for  the  growth  of  the  gas- 
bacillus  (B.  aerogenes  capsulatus) ,  the  bacteria  having 
been  thoroughly  spread  by  the  blood  through  the  body 
and  the  conditions  of  growth  being  highly  anaerobic. 
Welch  and  Nuttall  made  use  of  their  procedure  to  isolate 
the  gas-bacillus  and  to  demonstrate  its  ability  to  make  gas 
on  a  proteid  medium  containing  little  sugar.  The  bacil- 
lus of  rauschbrand  (symptomatic  anthrax)  also  induces 
the  conditions  obtained  by  the  gas-bacillus,  but  unlike 
the  gas-bacillus,  sporulates  under  these  conditions. 
The  bacilli  of  botulism  and  of  malignant  oedema  do  not 

1  "A  Gas-producing  Bacillus  (B.  aerogenes  capsulatus,  nov.  spec.) 
Capable  of  Rapid  Development  in  the  Blood  Vessels  after  Death," 
Butt,  of  the  Johns  Hopkins  Hosp.,  iii,  p.  81, 1892. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      119 

form  gas  in  the  incubated  rabbit,  but  induce  other  evi- 
dences of  putrefaction. 

It  seems  singular  that  almost  no  use  has  been  made  by 
subsequent  investigators  of  this  ingenious  and  extremely 
valuable  method  of  studying  the  gas-bacillus.  Acting 
on  the  suggestions  carried  by  the  paper  of  Welch  and 
Nuttall,  we  have  used  the  method  not  merely  as  an  aid 
in  the  identification  of  B.  aerogenes  capsulatus,  but  also 
(with  somewhat  unexpected  success)  as  a  means  of  deter- 
mining whether  the  gas-bacillus  is  present  in  considerable 
numbers  in  the  faeces. 

The  conditions  found  at  autopsy  after  twenty-four 
hours'  incubation  of  a  rabbit  previously  injected  intra- 
venously with  a  pure  culture  of  B.  aerogenes  capsu- 
latus have  been  so  fully  described  by  Professor  Welch 
that  it  is  unnecessary  to  add  anything  to  his  description 
aside  from  emphasizing  the  fact  that  the  almost  intoler- 
able odor  of  putrefaction  which  is  developed  during  the 
incubation  experiment  is  dependent  in  part  on  the  pro- 
duction of  butyric  or  a  closely  allied  acid.1  It  should 
also  be  added  that  an  odor  very  similar  to  that  charac- 
teristic of  the  incubation  experiment  can  be  observed  in 
the  faeces  of  some  persons  with  chronic  disturbances  of 
digestion,  and  frequently  in  persons  with  advanced  anae- 
mias associated  with  irregular  diarrhoeal  conditions. 

The  incubation  method  of  Welch  and  Nuttall  has 
apparently  never  been  employed  in  connection  with  the 

1 1  do  not  know  of  another  equally  impressive  example  of  the 
ability  of  microorganisms  to  induce  rapid  putrefactive  decompo- 
sition. 


120      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

study  of  the  human  faeces,  but  I  believe  it  has  here  an 
important  clinical  application.  Although  it  is  true  that 
B.  aerogenes  capsulatus  can  be  isolated  from  the  fseces 
of  a  majority  of  adult  individuals,  including  very  many 
who  are  in  excellent  health,  it  is  also  true  that  there  are 
wide  differences  in  the  number  of  capsulati  habitually 
present  in  the  case  of  different  individuals.  There  are 
some  young  persons  between  the  ages  of  five  and  twenty 
years  from  whom  it  is  either  very  difficult  to  obtain 
B.  aerogenes  capsulatus  by  plating  or  whose  movements 
give  no  evidence  whatever  of  its  presence.  If  we  pre- 
pare a  suspension  of  the  fseces  from  such  individuals  by 
grinding  one  gram  of  the  fresh  material  with  nine  cubic 
centimeters  of  0.85  per  cent,  salt  solution  and  filtering 
through  absorbent  cotton,  we  can  inject  intravenously 
one  or  two  cubic  centimeters  of  this  suspension  into  a 
rabbit  and  then  incubate  the  quickly  killed  rabbit  for 
five  hours  at  37°  C.  without  obtaining  evidence  of  the 
abundant  presence  of  the  gas-bacillus.  On  opening  a 
rabbit  which  has  been  thus  incubated,  one  finds  none  of 
the  signs  of  the  activity  of  the  gas-bacillus  —  no  accu- 
mulation of  gas  in  the  liver  or  vessels  or  in  the  con- 
nective tissues  or  serous  cavities.  Moreover,  smears  made 
from  the  liver  blood  or  the  auricular  blood  either  do  not 
show  the  presence  of  capsulatus  at  all,  or  these  organisms 
are  present  only  in  small  numbers.  If,  however,  the 
foregoing  experiment  be  made  with  the  fsecal  material 
derived  from  a  patient  with  pernicious  anaemia  or  from  a 
person  suffering  from  a  capsulatus  diarrhoea,  one  gener- 
ally gets  an  entirely  different  result.  At  the  end  of  five 


INFECTIONS  OF  THE  DIGESTIVE  TRACT       121 

hours  the  liver  is  soft  and  friable,  crepitates  between 
the  fingers,  and  on  section  shows  the  presence  of  many 
bubbles  of  gas.  There  may  also  be  a  small  accumulation 
of  gas  in  the  peritoneal  cavity.  Smears  from  the  he- 
patic blood  and  from  the  auricular  blood  swarm  with 
organisms  of  the  capsulatus  type.  The  spleen  also  con- 
tains such  organisms  in  great  numbers. 

The  following  protocols  are  instructive  in  this  con- 
nection :  — 

EXPERIMENT  1.  One  cubic  centimeter  of  a  filtered  faecal  suspen- 
sion, from  a  normal  person  sixteen  years  of  age,  almost  free  from 
putrefactive  products  in  the  urine,  was  injected  into  a  rabbit  which 
was  immediately  killed  by  a  blow  on  the  neck.  After  five  hours' 
incubation,  the  animal  was  examined.  Abdomen  distended  slightly 
from  distension  of  large  intestine;  liver  firm,  slightly  friable,  and 
free  from  gas.  A  stained  liver  smear  shows  a  few  short  bacilli 
(not  capsulatus} .  Heart's  blood  shows  short  bacilli  in  abundance, 
rarely  a  bacillus  of  capsulatus  type. 

EXPERIMENT  2.  Two  cubic  centimeters  of  filtered  faecal  sus- 
pension from  a  healthy  man  (aet.  42)  recently  recovered  from  uni- 
versal eczema,  were  injected  intravenously  into  a  rabbit  which 
was  then  promptly  killed  by  a  blow  on  the  neck.  Animal  incu- 
bated for  five  hours  at  37°  C.  On  exhibition,  no  odor  of  butyric 
decomposition;  liver  firm  and  without  gas  bubbles.  Smear  from 
heart's  blood  showed  a  few  bacteria  of  capsulatus  type. 

EXPERIMENT  3.  Two  cubic  centimeters  of  filtered  faecal  sus- 
pension from  a  healthy  breast-fed  baby  were  infused  intravenously 
into  a  rabbit  which  was  then  promptly  killed.  Examination  after 
five  hours'  incubation  at  37°  C.  reveals  no  odor  of  butyric  putre- 
faction, and  liver  is  firm  and  free  from  gas.  Smears  from  the 
heart's  blood  show  it  to  be  free  from  bacteria  of  any  kind. 

These  experiments  may  be  contrasted  with  the  follow- 
ing :  — 

EXPERIMENT  4.  Two  cubic  centimeters  of  filtered  faecal  sus- 
pension from  an  anaemic  baby  with  irregular  diarrhoea  were  in- 


122       INFECTIONS  OF  THE  DIGESTIVE  TRACT 

fused  intravenously  into  a  rabbit  which  was  then  promptly  killed 
and  incubated  for  five  hours  at  37°  C.  On  examination  the 
tissues  gave  a  strong  butyric  acid  odor.  Liver  soft,  friable,  and 
filled  with  bubbles  of  gas.  Smears  from  heart's  blood  show  a 
great  abundance  of  bacteria  of  the  capsulatus  type. 

EXPERIMENT  5.  One  cubic  centimeter  of  filtered  faecal  suspen- 
sion from  a  patient  with  pernicious  anaemia  was  infused  intra- 
venously into  a  rabbit  which  was  then  incubated  for  five  hours 
at  37°  C.  On  examination  the  abdomen  was  slightly  distended. 
Characteristic  butyric  odor.  Liver  crepitant,  contains  a  few  ob- 
vious gas  bubbles.  Bacilli  of  capsulatus  type  abundant  in  heart's 
blood,  in  almost  pure  culture.  Capsulati  also  abundant  in  liver. 

EXPERIMENT  6.  Two  cubic  centimeters  of  filtered  faecal  suspen- 
sion from  a  patient  with  pernicious  anaemia  whose  faeces  contained 
a  great  abundance  of  free  (capsulatus  ?)  spores  were  injected  intra- 
venously into  a  rabbit  which  was  incubated  at  37°  C.  for  twenty- 
four  hours.  At  autopsy  the  animal  was  greatly  distended  with  gas, 
and  bloody  fluid  was  oozing  freely  from  nose,  mouth,  etc.  Gas 
escaping  from  abdominal  cavity  burns  with  blue  flame.  Extremely 
offensive  odor  of  butyric  decomposition.  Tissues  in  advanced 
state  of  putrefactive  liquefaction.  Blood  from  heart  shows  bacilli 
of  capsulatus  type  to  be  extremely  abundant.  Most  of  these  were 
Gram-positive  and  occurred  characteristically  in  diplobacillus 
form,  but  there  were  also  many  long  threads  which  were  doubtless 
capsulati.  Gram-negative  forms  also  occur  and  of  these  one 
variety  was  especially  prominent.  This  was  a  long  organism 
bearing  a  large  spore  near  either  end.  It  is  probably  to  be  re- 
garded as  a  young  form  of  capsulatus  about  to  undergo  division 
midway  between  the  spores.  This  organism  was  Gram-negative. 


The  foregoing  experiments  are  typical  of  a  large  group 
and  show  plainly  enough  the  difference  in  capsulatus 
activity  in  the  case  of  material  derived  from  normal 
and  pathological  faeces.  It  appears  to  be  true  that  a 
ten  per  cent,  suspension  of  faeces  does  not  excite  an  active 
formation  of  gas  in  the  liver,  if  the  material  injected  has 
been  derived  from  persons  free  from  intestinal  derange- 
ments, and  with  scanty  evidences  of  putrefactive  pro- 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      123 

ducts  in  the  urine.  On  the  other  hand,  material  from 
persons  whose  stools  contain  an  abundance  of  capsulatus 
(including  a  large  proportion  of  persons  suffering  from 
"primary"  pernicious  ansemia)  induces  with  great 
regularity  the  peculiar  alterations  in  incubated  rabbits 
which  have  been  already  described.  The  short  period 
of  time  (four  to  six  hours)  which  is  required  to  bring 
about  the  liberation  of  gas  in  the  liver  is  a  point  worthy 
of  notice. 

The  distribution  of  B.  aerogenes  capsulatus  in  the 
bodies  of  rabbits  that  have  been  subjected  to  the  incu- 
bation test  is  a  matter  of  some  interest.  Where  normal 
rabbits  are  employed  for  this  test  one  finds  large  num- 
bers of  the  gas-bacillus  in  the  liver  and  often  considerable 
numbers  in  the  heart's  blood.  One  finds  also  moderate 
or  considerable  numbers  of  the  bacilli  in  the  spleen, 
where  they  have  doubtless  been  arrested  owing  to  me- 
chanical conditions.  In  the  brain,  in  the  suprarenals, 
in  the  kidneys,  and  in  other  organs,  one  finds  very  few 
gas-bacilli.  One  may  experimentally  change  somewhat 
the  distribution  of  these  organisms  if  previous  to  the 
injection  and  killing  of  the  rabbit  the  animal  be  fed  oh 
large  quantities  of  dextrose  —  say  twenty  grams  daily  for 
three  days.  Under  these  conditions,  if  the  inoculation 
test  be  carried  out,  it  will  be  found  that  not  only  do 
the  liver  and  blood  contain  much  larger  numbers  of  gas- 
bacilli  than  is  ordinarily  the  case,  but  the  spleen  also  con- 
tains great  numbers  of  the  same  organism.  Moreover, 
the  spleen  which  in  normal  rabbits  gives  no  gas,  will  be 
found  to  contain  numerous  bubbles  of  gas  and  therefore 


124      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

to  float  on  the  surface  of  water.  This  greatly  enhanced 
growth  of  the  gas-bacillus  in  animals  fed  upon  sugar  is 
doubtless  connected  with  the  increased  blood  content 
of  the  organism  in  glucose.  It  is  paralleled  by  the 
conditions  which  we  find  at  autopsy  in  persons  dying  of 
diabetes.  I  have  tried  to  rid  the  body  of  its  carbo- 
hydrates by  means  of  phlorhizin  poisoning  to  such  a 
point  that  the  growth  of  the  gas-bacillus  is  impaired  in 
the  incubation  test,  but  have  not  succeeded  in  distinctly 
altering  the  habitual  bacteria. 

The  selective  action  of  the  dead  organism  for  B.  aero- 
genes  capsulatus  is  certainly  a  striking  feature.  The  in- 
fusion of  any  faecal  suspension  means  the  introduction 
of  many  varieties  of  living  bacteria.  Yet  after  a  few 
hours  of  incubation  in  the  dead  rabbit  the  number  of 
microorganisms  in  the  blood  has  been  narrowed  either 
to  capsulatus  alone  or  to  capsulatus  and  one  of  two  com- 
panions—  often  positive  diplococci,  sometimes  spore- 
bearing  bacilli  resembling  capsulatus,  but  not  positively 
identified.  A  longer  period  of  incubation  usually  elimi- 
nates from  the  blood  all  organisms  except  those  of  the 
capsulatus  type.  The  initial  bactericidal  power  of  the 
blood  and  cell  juices  may  suffice  to  kill  many  of  the  bac- 
teria of  the  faeces,  while  the  strict  anaerobic  conditions, 
so  necessary  to  the  multiplication  of  capsulatus,  in  itself 
cuts  out  many  varieties. 

It  is  believed  that  the  more  refined  application  of  this 
method  to  the  study  of  the  faeces  will  prove  of  clinical 
value  in  several  directions.  It  may  also  prove  of  utility 
in  the  study  of  milk.  If,  as  seems  probable,  B.  aerogenes 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      125 

capsulatus  is  really  identical  with  the  granulo-badllus 
immobilis  liquefaciens  of  Grassberger  and  Schattenfroh 
(as  is  claimed  by  some  observers  and  denied  by  others, 
including  Fraenkel),  this  method  may  prove  helpful  in 
connection  with  the  study  of  some  diarrhoeal  diseases 
which  have  been  attributed  to  the  use  of  infected  milk. 

There  is  reason  to  think  that  the  faecal  suspensions 
from  most  persons  in  good  health  would  induce  gas  pro- 
duction in  incubated  rabbits,  since  the  faeces  of  most 
apparently  normal  persons  contain  moderate  numbers 
of  B.  aerogenes  capsulatus.  The  difference,  as  regards 
the  outcome  of  the  incubation  experiment,  between  the 
flora  of  these  persons  and  the  flora  of  persons  with  cap- 
sulatus infections  is  probably  one  of  degree  and  not  of 
kind.  Some  idea  of  the  relative  numbers  of  capsulati 
present  might  perhaps  be  gained  by  determining  the  small- 
est volume  of  a  given  fsecal  suspension  that  will  just  suf- 
fice to  induce  the  distinctive  gas  production  in  incubated 
rabbits  within  a  given  time. 

As  it  was  obviously  impracticable  to  isolate  in  every 
instance  the  dominant  microorganisms  of  the  faeces,  it 
was  resolved  to  study  the  action  of  the  mixed  faecal  flora. 
This  was  done  in  the  hope  of  obtaining  information  which 
should  be  of  service  in  determining  what  bacteria  are 
really  dominant  in  the  intestine.  The  effort  has  not 
been  wholly  successful,  but  has,  nevertheless,  proved 
useful  in  several  ways.  A  suspension  of  the  mixed  flora 
was  prepared  in  normal  salt  solution  in  the  proportion 
of  about  one  part  of  material  by  weight  to  ten  parts 
of  the  solution.  From  this  suspension  a  series  of 


126      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

fermentation  tubes  was  inoculated  in  a  uniform  manner. 
The  fermentation  tubes  contained  dextrose  bouillon, 
levulose  bouillon  (made  with  Schering's  diabetin),  lactose 
bouillon,  saccharose  bouillon,  peptone  bouillon  and  plain 
bouillon,  litmus  milk,  dextrose  bouillon  containing  methyl- 
ene  blue,  dextrose  bouillon  containing  neutral  red,  and 
dextrose  bouillon  containing  methyl  violet.  The  tubes 
containing  the  dyes  were  employed  to  determine  the 
reducing  activity  of  the  bacteria.  As  the  information 
yielded  by  these  color  tubes  did  not  appear  especially 
helpful,  the  method  was  temporarily  abandoned.  Far 
more  useful  was  the  study  of  the  gas  production  in  the 
sugar-bouillon  tubes.  These  tubes  contained  concen- 
trations of  the  sugars  already  mentioned  equal  to  two 
per  cent,  in  each  case.  It  was  found  that  the  least 
gas  was  usually  obtained  on  the  saccharose  medium, 
and  the  most  on  the  dextrose  or  lactose.  The  quantity 
of  gas  produced  in  conditions  of  health  by  the  mixed 
flora  is  somewhat  variable,  but  may  be  roughly  stated 
as  varying  ordinarily  from  fifteen  to  thirty  per  cent, 
of  the  height  of  the  anaerobic  limb.  This  estimate  is 
based  not  on  any  one  sugar  tube,  but  on  the  average  of 
the  four  tubes,  the  gas  production,  as  already  stated, 
having  been  unequal  in  these  different  tubes.  In  normal 
children  on  a  milk  diet  the  gas  production  is  often  some- 
what less  than  in  adults  and  may  be  not  more  than  ten 
to  fifteen  per  cent.  In  conditions  of  disease  the  gas 
production  was  found  to  be  usually  considerably  less 
than  the  average  production  in  health.  This  is  true 
both  of  adults  and  of  children.  In  the  case  of  well- 


INFECTIONS  OF  THE  DIGESTIVE  TRACT       127 

marked  examples  of  saccharo-butyric  putrefaction  the 
quantity  of  gas  produced  may  be  one-half,  one-third, 
one-quarter,  or  even  one-fifth  of  the  normal  gas  produc- 
tion. I  am  disposed  to  attribute  this  mainly  or  wholly 
to  an  elimination  of  the  colon  bacilli.  The  gas  produc- 
tion in  the  sugar-bouillon  tubes  has  in  several  instances 
been  observed  to  correspond  fairly  closely  to  the  volume 
of  gas  produced  by  the  colon  bacilli  from  the  same  case. 
It  is  known  that  different  strains  of  colon  bacilli  liberate 
different  quantities  of  gas  on  the  same  sugar-bouillon 
medium,  and  I  am  therefore  disposed  to  attribute 
the  fluctuations  observed  in  health  mainly  to  the  different 
gas-producing  character  of  organisms  of  the  colon  bacillus 
group.  It  is  possible  that  B.  lactis  aerogenes  plays  a 
part,  but  I  believe  this  organism  to  have  a  subordinate 
role.  There  are  cases  in  which  the  intestine  contains 
yeast  organisms,  and  under  these  circumstances  there 
is  a  very  much  larger  gas  production  than  is  ordinarily 
the  case.  A  very  abundant  gas  production  in  the  sugar- 
bouillon  tubes  inoculated  from  the  faecal  flora  should 
excite  suspicion  of  the  presence  of  yeasts.  Sometimes, 
however,  the  excessive  gas  production  is  dependent  on 
the  growth  of  B.  lactis  aerogenes.  As  I  have  already 
stated,  this  organism  in  pure  culture  does  not  ordinarily 
grow  in  the  closed  limb  of  the  fermentation  tube,  and 
in  order  to  enable  it  to  grow  it  has  to  be  aided  by  the 
presence  of  blood  or  bits  of  sterile  tissue.  We  have 
observed  instances,  however,  in  which  B.  aerogenes  cap- 
sulatus  has  grown  in  the  closed  limb  of  the  fermentation 
tube  without  the  addition  of  tissue,  and  I  attribute  this 


128      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

to  the  transference  to  the  tube  of  some  nutritive  sub- 
stance contained  in  the  intestine. 

By  far  the  greatest  value  of  the  gas  production  in  the 
fermentation  tubes  is  in  those  cases  in  which  the  gas 
production  is  much  below  normal.  This  diminution  in 
gas  formation  is  not  a  variable  occurrence,  but  in  the 
case  of  the  same  individual  is  persistent  so  long  as  the 
conditions  of  diet  and  habits  of  life  remain  the  same. 
It  is,  in  fact,  an  individual  peculiarity.  As  already 
stated,  it  appears  to  depend  on  the  elimination  of  typical 
colon  bacilli.  This  view  has  been  supported  repeatedly 
by  the  results  of  plating  upon  litmus  gelatin.  The  dis- 
appearance of  the  colon  bacilli  is  occasionally  met  with 
in  persons  apparently  in  good  health,  but  I  believe  this 
to  be  a  very  exceptional  occurrence.  Ordinarily  the 
inability  to  produce  gas  in  normal  abundance  is  a  sign 
of  a  temporary  or  persistent  alteration  in  the  character 
of  the  intestinal  flora.  There  are  instances,  indeed,  in 
which  we  have  been  unable  to  obtain  any  gas  whatever 
in  some  or  all  of  the  sugar-bouillon  tubes.  These  have 
been  usually  instances  of  an  extremely  marked  form  of 
saccharo-butyric  putrefaction  and  have  not  been  very 
uncommon  among  cases  of  pernicious  anaemia  associated 
with  an  infection  with  B.  aerogenes  capsulatus  and  the 
disappearance  of  the  colon  bacilli.  This  disappearance 
has  been  noted  also  in  some  cases  of  mucous  colitis 
in  which  a  foreign  race  of  colon  bacilli  (or  organisms 
intermediate  between  colon  bacilli  and  typhoid  or  para- 
typhoid bacilli)  have  been  found  to  be  the  dominant 
representatives  of  the  colon  bacillus  group. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT       129 

The  influence  of  diet  must  not  be  overlooked  in  con- 
nection with  the  question  of  gas  production  in  the  fer- 
mentation tubes  by  the  mixed  faecal  flora.  It  seems 
probable  that  a  diet  containing  an  abundance  of  carbo- 
hydrates leads  to  greater  gas  production  than  a  diet  in 
which  carbohydrates  are  much  restricted.  A  patient 
on  a  diet  consisting  chiefly  of  meat  will  harbor  organisms 
making  less  gas  than  if  he  were  on  a  mixed  diet.  The  fall 
in  gas  on  a  meat  diet  may  amount  to  forty  or  fifty  per 
cent,  of  the  total  gas  production  on  a  mixed  diet,  perhaps 
in  some  cases  to  more  than  this.  This  factor  is  thus  one 
which  must  be  taken  into  consideration  in  interpreting 
the  results  of  the  gas  production  by  the  mixed  faecal 
flora. 

From  the  peptone-bouillon  tube  it  is  possible  by 
means  of  the  Ehrlich  dimethylamidobenzaldehyde  re- 
action to  form  a  rough  estimate  of  the  abundance  of  the 
indol  formed.  Some  idea  of  the  quantity  of  ammonia 
and  other  volatile  bases  produced  may  be  obtained  by 
the  use  of  Nessler's  reagent.  By  diluting  the  bouillon 
and  using  definite  quantities  of  Nessler's  reagent  in 
making  the  tests,  one  may  gain  some  idea  as  to  quantita- 
tive differences  in  regard  to  the  production  of  bases. 
The  addition  of  strong  hydrochloric  acid  to  the  peptone- 
bouillon  tube  causes  in  some  cases  a  liberation  of  sul- 
phureted  hydrogen,  which  collects  in  the  upper  portion 
of  the  closed  limb  and  may  give  an  indication  of  an  un- 
usual formation  of  this  gas.  That  it  is  mainly  or  wholly 
hydrogen  sulphide  that  collects  under  these  circumstances 
is  shown  by  the  fact  that  the  addition  of  a  solution  of 


130       INFECTIONS  OF  THE  DIGESTIVE  TRACT 

an  iron  or  cadmium  salt  leads  to  the  reabsorption  of 
the  sulphur  compound,  giving  rise  to  sulphides  of  the 
metals. 

In  some  cases  fermentation  tubes  containing  bouillon 
(or  sugar  bouillon)  have  had  added  to  them  calcium  or 
magnesium  carbonate.  By  maintaining  the  neutrality 
of  the  culture  medium  the  carbonates  have  influenced 
the  character  of  the  dominant  organisms  in  the  fermen- 
tation tubes  and  have  thus  modified  the  proportions  of 
the  products  formed  and  even  to  some  extent  their 
character. 

It  has  been  found  useful  to  examine  regularly  the 
sediments  of  the  fermentation  tubes  which  have  been 
inoculated  with  the  mixed  fa?cal  flora.  This  has  been 
done  as  a  matter  of  routine  in  a  large  number  of  in- 
stances, the  examination  having  been  made  especially 
in  the  case  of  the  four  sugar-bouillon  tubes  and  the 
peptone-bouillon  tube.  The  appearance  of  the  Gram- 
stained  flora  gives  as  a  rule,  but  not  always,  an  indication 
of  the  dominant  flora  in  the  lower  part  of  the  intestine. 
In  tubes  inoculated  from  normal  persons,  Gram-negative 
organisms  corresponding  in  size  and  form  to  bacteria  of 
the  B.  coli  type  grow  abundantly  in  all  the  tubes.  As 
a  rule  they  constitute  the  dominant  flora  in  all  the  sedi- 
ments. Generally  one  sees  mixed  with  them  moderate 
numbers  of  Gram-positive  and  Gram-negative  diplo- 
cocci.  Moderate  numbers  of  organisms  morphologically 
like  B.  aerogenes  capsulatus  are  seen,  but  these  forms 
may  be  wholly  absent.  There  is  an  aerobic,  Gram- 
positive  bacillus,  resembling  closely  in  its  morphology 


INFECTIONS  OF  THE  DIGESTIVE  TRACT       131 

the  anaerobe  just  mentioned,  and  the  two  organisms 
can  be  positively  distinguished  only  by  making  blood- 
agar  cultures  under  aerobic  and  anaerobic  conditions. 
The  growth  of  the  organisms  is  usually  slighter  in  a 
sugar-free  tube  than  in  the  ones  containing  sugar.  The 
diplococcal  forms,  especially,  are  apt  to  grow  poorly 
in  the  peptone  bouillon  and  may  quite  fail  to  multiply. 
In  material  containing  large  numbers  of  the  plain  form 
of  B.  bifidus  one  finds  in  the  sugar  tubes  large  numbers 
of  this  organism  in  its  bifid  form.  Very  beautiful 
branching  forms,  presenting  considerable  variety  in 
their  morphology,  may  be  observed.  One  has  this  ex- 
perience especially  with  the  lactose  and  dextrose  bou- 
illon, and  I  think  the  growths  of  Hfidus  are  apt  to  be 
especially  luxuriant  in  the  lactose-bouillon  tube.  The 
so-called  punctate  form  already  described  is  very  com- 
mon in  the  fermentation  tubes. 

Under  pathological  conditions  one  may  meet  with 
different  bacterial  elements  in  the  sediments.  In  cases 
in  which  the  intestine  contains  large  numbers  of  positive 
diplococci  or  streptococci,  there  is  an  abundant  growth 
of  positive  diplococcus  forms  and  streptococcus  forms  in 
the  sugar  tubes.  One  may  find  streptococcus  forms  very 
abundant  even  hi  cases  where  the  tubes  have  been  inocu- 
lated from  flora  not  containing  a  strikingly  increased 
number  of  such  bacteria.  As  a  rule  a  .very  great  pre- 
ponderance of  streptococcal  and  diplococcal  forms  in  the 
fermentation  tubes  points  to  an  excess  of  such  organisms 
in  the  digestive  tract.  By  the  use  of  this  method  atten- 
tion has  sometimes  been  drawn  to  this  -type  of  bacterial 


132      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

activity  in  the  digestive  tract  where  it  would  otherwise 
have  been  overlooked.  In  some  instances,  also,  one 
sees  a  great  development  of  anaerobes  in  the  fermentation 
tubes.  Sometimes  one  sees  sedimentary  fields  which 
consist  wholly  of  streptococcal  forms  and  of  forms  which 
are  probably  B.  aerogenes  capsulatus.  This  has  been 
repeatedly  noticed  in  some  cases  of  advanced  chronic 
saccharo-butyric  putrefaction  with  an  extreme  degree 
of  ansemia.  The  tendency  for  the  organisms  of  the  B. 
coli  type  to  be  poorly  represented  in  cases  of  chronic 
saccharo-butyric  putrefaction  is  evident  in  the  sediment 
of  the  fermentation  tubes.  In  some  cases  one  finds  that 
the  fermentation  tubes  develop  a  greenish  color  in  the 
open  aerobic  arm  of  the  tube  and  also  a  greenish  pellicle. 
Culture  shows  this  to  be  due  to  the  B.  pyocyaneus. 
This  organism  has  been  found  in  only  a  small  number  of 
cases  and  usually,  but  not  always,  in  persons  presenting 
signs  of  digestive  disorder. 

It  cannot  be  claimed  that  we  now  know  the  full  value 
or  the  limitations  of  the  information  to  be  derived  from 
the  careful  study  of  the  sediments  of  the  fermentation 
tubes,  but  it  may  safely  be  said  that  this  method  of 
investigation  has  often  been  helpful  in  gaining  a  clew  to 
the  nature  of  the  dominant  organisms  in  the  intestinal 
tract.  One  cannot  rely  upon  it  alone,  but  in  connection 
with  data  derived  from  other  methods  it  helps  us  to 
form  a  conception  of  the  bacterial  types  present  and 
active  in  the  lower  part  of  the  digestive  tract.  One 
finds  in  the  same  case  almost  regularly  the  same  kinds  of 
sediments,  and  this  gives  a  degree  of  confidence  hi  the 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      133 

value  of  the  sediments,  as  an  indication  of  the  well-de- 
fined character  of  the  bacterial  conditions  that  give  rise 
to  these  individual  peculiarities.  A  highly  interesting 
observation  which  has  been  repeatedly  made  is  that  the 
character  of  the  sediments  may  be  greatly  altered  as  a 
patient  grows  better  or  develops  a  more  intense  degree 
of  a  condition  from  which  he  is  suffering.  The  gradual 
reappearance  of  the  colon  bacilli  in  the  sedimentary 
fields,  with  the  corresponding  disappearance  of  an  exces- 
sive number  of  coccal  and  streptococcal  forms  and  of 
anaerobes,  has  repeatedly  been  noticed  as  a  concomitant 
of  a  pronounced  improvement  in  clinical  conditions.  In 
addition  to  the  study  of  the  mixed  faBcal  flora  (as  grown 
upon  fermentation  tubes)  many  observations  have  now 
been  made  upon  larger  volumes  of  media  in  which  the 
mixed  flora  has  grown  for  relatively  long  periods  of  time, 
usually  a  week.  As  a  routine  procedure  in  the  investiga- 
tion of  many  normal  persons  and  numerous  pathological 
conditions,  four  flasks  containing  about  five  hundred 
cubic  centimeters  each  of  medium  have  been  inoculated 
with  the  suspensions  of  the  mixed  flora.  The  media  em- 
ployed have  been  peptone  bouillon,  peptone  bouillon  with 
calcium  carbonate,  sugar  bouillon  and  sugar  bouillon 
with  calcium  carbonate.  The  organisms  have  been  per- 
mitted to  grow  for  a  period  of  seven  days.  Under  the 
conditions  prevailing  in  these  flasks  a  large  part  of  the 
growth  has  been  anaerobic  and  a  high  degree  of  anaero- 
biosis  has  been  maintained,  in  part  owing  to  the  forma- 
tion of  reducing  products  such  as  hydrogen,  which  are 
incidental  to  the  development  of  fermentative  and 


134      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

putrefactive  cleavages.  Two  objects  have  been  served 
through  the  employment  of  these  flask  cultures:  first, 
the  study  of  the  bacterial  sediments  after  considerable 
periods  of  growth;  and,  secondly,  the  study  of  the  pro- 
ducts formed  on  a  representative  medium.  As  regards 
the  characters  of  the  organisms  found  in  the  sediments 
(at  the  end  of  seven  days)  it  is  not  possible  at  present  to 
state  definitely  to  what  extent  the  biochemistry  of  the 
digestive  tract  can  be  furthered  by  the  mere  study  of  the 
Gram-stained  fields,  without  resort  to  cultural  methods 
permitting  positive  identification  of  the  dominant  forms. 
The  appearances  in  the  flasks  usually  vary  considerably 
with  the  different  media  employed  and  also  according 
to  the  origin  of  the  suspensions  employed  for  inoculation. 
It  has  been  found,  in  general,  that  the  anaerobes  grow 
more  abundantly  in  the  flasks  in  which  a  neutral  re- 
action is  maintained,  owing  to  the  presence  of  calcium 
carbonate.  Whether  the  presence  of  calcium  ions  as 
such  influences  the  growth  of  the  organisms  in  a  specific 
way  is  not  known.  It  is  certain  that  hi  some  cases  of 
excessive  intestinal  putrefaction  attention  has  been 
called  to  the  prolific  growth  of  certain  anaerobes  which 
have  been  much  less  prominent  in  the  intestinal  con- 
tents themselves  and  in  the  sediments  of  the  fermenta- 
tion tubes  (in  which  the  suspended  bacteria  have  been 
permitted  to  grow  for  a  considerably  shorter  time  than 
in  the  flasks).  In  several  instances  microorganisms  of 
the  morphological  type  of  B.  putrificus  have  been  ex- 
tremely abundant  in  the  sediments  of  the  calcium-car- 
bonate flasks.  Later  it  has  been  noticed  in  some  of 


INFECTIONS  OF  THE  DIGESTIVE  TRACT       135 

these  cases  that  the  growth  of  what  we  may  assume  to 
have  been  B.  putrificus  is  no  longer  evident,  and  this 
change  in  the  character  of  the  growths  in  the  flasks  has 
corresponded  to  a  clinical  improvement  in  the  condition  of 
the  patients  concerned.  As  regards  B.  aerogenes  capsula- 
tus,  it  cannot  be  said  that  we  have  learned  more  from  the 
seven-day  flasks  than  from  the  fermentation  tube  sedi- 
ments already  mentioned.  In  a  few  instances  it  has 
been  observed  that  the  peptone-bouillon  flask  has  con- 
tained enormous  numbers  of  spores  when  the  corre- 
sponding calcium-carbonate  flask  has  shown  large  num- 
bers of  vegetative  forms  of  putrefactive  microorganisms 
and  relatively  few  spores.  Further  studies  are  neces- 
sary to  determine  the  value  of  the  seven-day-flask 
method  and  to  show  how  the  bacterial  fields  are  to  be 
interpreted. 

The  chemical  examination  of  the  seven-day  flasks 
has  included  two  different  series  of  procedures.  In  the 
case  of  the  peptone-bouillon  flask  and  the  peptone- 
bouillon  flask  containing  calcium  carbonate,  the  con- 
tents have  been  examined  with  respect  to  hydrogen 
sulphide,  methyl  mercaptan,  volatile  fatty  acids,  am- 
monia, indol,  skatol,  and  phenol.1  Quantitative  deter- 

1  A  number  of  observations  have  been  made  upon  the  bouillon 
and  bouillon-carbonate  flasks  inoculated  from  the  mixed  flora 
with  a  view  to  determining  whether  indol  acetic  acid  is  ever  formed. 
The  method  consisted  in  applying  the  three  tests  of  Salkowski 
to  the  material  which  remains  behind  after  the  distillation  of 
indol  and  skatol.  In  one  case  only  has  this  residual  material  given 
reactions  with  the  three  tests  of  Salkowski.  This  was  in  the  case 
of  flasks  prepared  from  a  patient  with  peripheral  neuritis  and 
pronounced  psychosis  resembling  that  of  alcoholic  intoxication. 


136      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

minations  have  regularly  been  made  in  the  case  of  the 
volatile  fatty  acids,  ammonia,  indol,  skatol,  and  phenol. 
Alcohol  and  acetone  have  also  been  tested  for  in  these 
flasks.  In  the  case  of  the  sugar-bouillon  flasks  the 
contents  have  been  examined  for  alcohol,  acetone,  the 
volatile  fatty  acids,  and  the  non-volatile  organic  acids. 
The  molecular  weight  of  the  barium  salts  of  the  volatile 
fatty  acids  has  regularly  been  determined  in  order  to 
obtain  a  conception  of  the  chemical  nature  and  quantity 
of  the  chief  fatty  acids  produced.  The  interesting  ob- 
servation has  been  made  that  in  the  flasks  containing 
calcium  carbonate  the  molecular  weight  obtained  for 
the  volatile  fatty  acids  has  nearly  always  been  some- 
what higher  than  in  the  case  of  the  molecular  weight 
obtained  from  the  volatile  fatty  acids  of  the  sugar- 
bouillon  flasks.  This  fact  corresponds  to  the  appearances 
in  the  smears  (already  noted)  that  putrefactive  anaerobes 
are  found  in  greater  abundance  in  the  neutral  flasks 
than  in  the  sugar-bouillon  flasks  to  which  calcium  car- 
bonate has  not  been  added. 

The  fact  that  acetone  has  been  found  in  many  instances 
in  the  flasks  containing  peptone  bouillon  and  peptone 
bouillon  with  the  addition  of  calcium  carbonate  will  be 
referred  to  in  reviewing  the  facts  regarding  the  nature 
of  the  products  of  fermentative  putrefactive  decomposi- 
tion. 

The  method  employed  to  determine  the  presence  of 

2 

In  this  case,  however,  alcoholic  intoxication  could  be  almost 
certainly  excluded.  There  were  various  other  indications  that 
the  neuritis  and  psychosis  were  due  to  intestinal  intoxications. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT       137 

methyl  mercaptan  is  as  follows:  One  hundred  cubic 
centimeters  of  the  culture  to  be  examined  are  trans- 
ferred to  a  flask  communicating  through  a  calcium 
chloride  tube  with  an  Erlenmeyer  flask  containing 
isatin  dissolved  in  concentrated  sulphuric  acid.  A 
current  of  air  is  then  drawn  through  both  flasks  so 
that  any  mercaptan  given  off  from  the  culture  flask 
will  enter  the  isatin-sulphuric-acid  flask.  The  pres- 
ence of  mercaptan  is  indicated  under  these  conditions 
by  a  gradual  change  of  the  isatin  solution  from  red  to 
olive-green  or  grass-green.1  In  order  to  save  isatin 
the  reaction  may  be  carried  out  substituting  a  test- 
tube  containing  about  ten  cubic  centimeters  of  the 
isatin-sulphuric-acid  mixture  for  the  Erlenmeyer  flask. 
The  method  is  not  adapted  for  quantitative  deter- 
minations, but  some  idea  can  be  gained  through  it 
of  the  quantity  of  mercaptan  present  in  the  culture,  and 
it  further  serves  to  indicate  differences  in  the  amount 
formed  in  different  cultures.  Twenty-five  milligrams  of 
a  one  per  cent,  solution  of  methyl  mercaptan  suffice 
gradually  to  alter  the  isatin  red  solution  (about  fifty  cubic 
centimeters)  to  a  deep  green  in  the  course  of  ten  minutes. 
Reactions  as  strong  as  this  are  occasionally  obtained 
from  one  hundred  cubic  centimeters  of  a  bacterial  cul- 
ture in  the  course  of  five  or  ten  minutes.  Frequently 

1  This  method  has  been  used  by  Niemann,  ("Ueber  die  Abspal- 
tung  von  Kohlensaure,  Mercaptan  und  Schwefelwasserstoff  beim 
Kochen  einiger  animalischen  und  vegetabilischen  Nahrungsmittel," 
Archiv  f.  Hyg.,  xix,  p.  126,  1893);  also  by  Bauer,  ("Ueber  die 
Einwirkung  gespannter  Wasserdampfe  auf  Keratin,"  Zeitschr.  f. 
physiol.  Chem.,  xxxv,  p.  346,  1902). 


138      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

one  obtains  after  the  lapse  of  fifteen  minutes  only  a 
browning  of  the  isatin-sulphuric-acid  solution  with  no 
definite  appearance  of  a  green  tint.  This  appearance  is 
probably  to  be  interpreted  as  dependent  on  a  mere  trace 
of  methyl  mercaptan. 

The  method  used  for  the  determination  of  indol 
obtained  from  distillation  of  putrefactive  mixtures  is 
that  based  on  the  formation  of  a  color  compound  due  to 
the  combination  of  two  molecules  of  indol  with  one 
molecule  of  /3-napthaquinone-sodium-monosulphonate. 
This  method  has  proved  in  a  high  degree  serviceable 
and  may  be  recommended  on  account  of  its  accuracy 
and  quickness.  The  main  features  of  this  method 
are  as  follows:  — 

The  method  is  dependent  upon  the  almost  quantitative 
precipitation  of  indol  in  alkaline  solution  by  a  dilute 
solution  of  /3-naphthaquinone-sodium-monosulphonate. 
A  dilute  solution  of  indol  (1 :  500,000  parts  of  water) 
made  slightly  alkaline  with  potassium  hydroxide,  gives 
with  one  drop  of  a  two  per  cent,  solution  of  /3-naph- 
thaquinone-sodium-monosulphonate  a  blue  or  green-blue 
color.  A  more  concentrated  solution  of  indol  will  give 
a  precipitate  which  upon  examination  will  be  found  to 
consist  of  well-defined  acicular  needles,  bluish  in  color 
and  closely  felted  together.  The  compound,  evident 
either  as  precipitate  or  as  coloration,  is  completely 
soluble  in  chloroform,  with  the  production  of  a  red  color. 
From  this  extract  the  indol  may  be  determined  quantita- 
tively either  by  evaporating  the  chloroform  or  by  match- 
ing the  color  to  a  standard  in  the  Duboscq  colorimeter. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      139 

A  slight  blue  precipitate  forms  in  solutions  containing 
one  part  of  indol  to  256,000  parts  of  water;  in  greater 
dilution  the  coloration  is  green,  and  fails  entirely  when 
the  dilution  is  1 :  1,024,000  parts.  Even  in  this  extreme 
dilution  chloroform  will  indicate  the  presence  of  the  di- 
indyl  -  di  -  hy  dronaphthalme  -  keto  -  sodium  -  monosulpho- 
nate  by  its  faintly  pink  color.  The  reaction  is  essentially 
a  time  reaction,  and  even  in  dilute  solution  it  has  been 
found  desirable  to  allow  a  period  of  not  less  than  ten 
minutes  to  elapse  before  shaking  out  the  condensation 
product  with  chloroform.  The  naphthaquinone  solution 
should  be  added  in  sufficient  excess  to  tinge  the  filtrate 
slightly  yellow. 

As  indol  is  sometimes  associated  in  the  course  of  putre- 
faction with  skatol  (and  this  is  not  uncommonly  so  in 
the  case  of  the  contents  of  the  large  intestine),  it  becomes 
important  to  have  a  method  for  the  separation  of  indol 
and  skatol.  These  putrefactive  decomposition  products 
may  be  separated  by  means  of  their  picrates,  but  the 
method  involves  so  much  time  as  to  make  it  unfit  for 
clinical  or  ordinary  chemical  investigations.  It  is 
believed  that  the  method  described  by  Herter  and 
Foster  l  will  prove  useful  in  effecting  the  quick  and  nearly 
complete  separation  of  indol  from  skatol.  Moreover, 
this  method  serves  also  for  the  determination  of  the 
quantity  of  skatol  present. 

The  procedure  is  based  on  the  fact  that  by  means  of 
the  naphthaquinone  method  for  indol  which  has  just 

1  "  On  the  Separation  of  Indol  from  Skatol  and  their  Quanti- 
tative Determination,"  Journ.  Biol.  Chem.,  II,  p.  267,  1906. 


140      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

been  described,  it  is  possible  to  remove  almost  completely 
the  indol  from  a  solution  containing  both  indol  and  skatol 
and  that  the  skatol  remaining  after  the  removal  of 
the  indol  can  be  distilled  and  recognized  by  means  of 
the  dimethylamidobenzaldehyde  reaction  described  by 
Ehrlich.  If  one  takes  a  putrefactive  mixture  containing 
both  indol  and  skatol,  these  bases  should  first  be  dis- 
tilled either  in  acid  or  alkaline  solution  —  preferably 
with  the  aid  of  steam  if  the  quantities  are  considerable. 
In  the  distillate  the  skatol  passes  over  earlier  than  the 
indol,  as  can  easily  be  shown  by  means  of  the  blue  color 
which  it  gives  on  boiling  with  Ehrlich's  aldehyde.  To 
the  distillate  containing  the  indol  enough  sodium 
or  potassium  hydroxide  is  added  to  render  it  slightly 
alkaline.  An  excess  of  the  /3-naphthaquinone-sodium- 
monosulphonate  is  now  added  to  this  solution.  As 
already  described,  this  substance  in  the  course  of  a  few 
minutes  reacts  almost  completely  with  the  indol  present, 
but  not  with  the  skatol.  The  blue  or  purplish-blue 
precipitate  of  the  newly  formed  indol-naphthaquinone 
compound  is  now  removed  by  filtration.  In  cases  where 
the  concentration  of  indol  is  too  small  to  give  rise  to 
a  precipitate  when  treated  with  the  naphthaquinone 
compound  the  solution  simply  develops  a  green  or 
greenish-blue  color.  The  solution  is  now  acidified  and 
subjected  to  distillation,  with  or  without  the  use  of  steam. 
The  skatol  passes  over  into  the  distillate,  whereas  the  in- 
dol is  held  back  in  the  form  of  the  indol-naphthaquinone 
compound,  with  the  exception  of  a  very  small  uncom- 
bined  portion,  which  passes  over  with  the  skatol.  The 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      141 

amount  of  indol,  however,  which  passes  over  after  treat- 
ment with  the  /3-naphthaqumone-sodium-monosulpho- 
nate  is  so  small  that  it  is  practically  negligible,  although 
its  presence  is  detectable  through  the  red  color  which  it 
gives  when  acted  upon  by  dimethylamidobenzaldehyde. 
The  distillate  containing  skatol  is  boiled  with  a  solution 
of  Ehrlich's  aldehyde  in  sulphuric  acid.1  A  slight  amount 
of  dilute  hydrochloric  acid  is  now  added  and  has  the 
effect  of  intensifying  the  blue  color  produced  by  boiling 
the  skatol  with  the  Ehrlich  aldehyde  solution.  A  little 
experience  is  required  to  find  the  amount  of  hydro- 
chloric acid  which  gives  the  maximal  intensification  of 
the  reaction.  An  excess  of  hydrochloric  acid  causes  the 
blue  color  to  fade.  It  is  important  to  use  an  excess  of  the 
Ehrlich  aldehyde  solution  in  order  to  develop  fully  the 
color  reaction  with  skatol.  The  color  obtained  through 
the  action  of  Ehrlich's  aldehyde  upon  skatol  is  purple- 
blue  rather  than  blue  so  long  as  the  solution  is  hot. 
On  cooling  it  under  the  tap,  the  blue  color  asserts  itself 
more  strongly,  and  the  solution  may  become  some- 
what opalescent  from  the  separation  of  uncombined 
dimethylamidobenzaldehyde.  Chloroform  is  now  added 
to  the  solution  containing  the  blue  product.  On  agita- 
tion with  the  solution  this  carries  out  the  blue  color, 
and  the  chloroform  assumes  a  pure  blue  tint.  By  means 
of  a  good  colorimeter  the  quantity  of  skatol  present 
in  the  original  solution  may  be  approximated  by  the 
intensity  of  the  color  reaction. 
On  evaporating  the  chloroform  containing  the  blue 
1  Five  per  cent,  aldehyde  in  ten  per  cent,  sulphuric  acid. 


142      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

color  resulting  from  the  action  of  the  dimethylamido- 
benzaldehyde  on  skatol,  one  obtains  an  amorphous  blue 
material  which  can  be  partially  purified  from  the  ad- 
mixture with  Ehrlich's  aldehyde  by  the  use  of  petroleum 
ether.  The  nature  of  this  compound  is  not  at  present 
known.  The  melting  point  of  our  preparation  lay  be- 
tween 65°  C.  and  66°  C. 

The  method  of  separating  indol  and  skatol  here  de- 
scribed has  been  used  in  a  routine  way  during  the  past 
year  in  connection  with  the  study  of  the  faeces  and  has 
given  satisfaction.  To  twenty-five  grams  of  the  mate- 
rial have  been  added  twenty  cubic  centimeters  of  water 
and  one  to  two  cubic  centimeters  of  a  ten  per  cent, 
sodium  hydroxide  solution.  The  suspension  is  then 
subjected  to  distillation  with  the  aid  of  steam,  until  the 
distillate  no  longer  gives  a  color  reaction  when  boiled 
with  the  dimethylamidobenzaldehyde  solution.  Ordina- 
rily the  indol  and  skatol  present  go  over  completely  within 
an  hour,  but  where  the  material  develops  frothing  a  more 
prolonged  distillation  may  be  necessary.  When  the 
distillate  has  been  obtained,  it  is  treated  in  the  manner 
above  outlined  for  the  separation  of  indol  and  skatol. 
In  some  cases  one  obtains  only  skatol  from  the  faeces, 
but  as  a  rule  indol  is  also  present.  In  the  presence  of 
indol  the  chloroform  extract,  instead  of  being  a  pure 
blue,  may  have  a  slightly  purplish  tinge,  owing  to  una- 
voidable admixture  with  a  slight  amount  of  indol. 

It  is  important  in  making  the  colorimetric  estimations 
of  the  quantity  of  skatol  present  to  employ  a  standard 
color  solution  for  comparison  with  the  color  obtained 


INFECTIONS  OF  THE  DIGESTIVE  TRACT       143 

from  the  distillate  containing  the  skatol.  Various  dyes 
have  been  tried  with  a  view  to  obtaining  a  standard 
solution  which  will  retain  its  color  unchanged.  Ex- 
perience has  shown  that  the  best  standard  color  solution 
is  one  obtained  from  a  solution  of  skatol.  Although 
such  a  solution  fades  after  a  few  days,  especially  when 
exposed  to  the  light,  and  may  assume  a  greenish  tint, 
in  the  dark  it  may  last  several  weeks  without  undergoing 
appreciable  change.  Moreover,  as  the  skatol  standard 
solution  is  readily  prepared,  there  is  little  disadvantage 
from  being  compelled  to  renew  the  color  solution  from 
time  to  time.  This  solution  may  be  conveniently  pre- 
pared by  dissolving  five  milligrams  of  skatol  in  water  and 
acting  upon  it  with  an  excess  of  dimethylamidobenzalde- 
hyde.  It  commonly  requires  from  one  hundred  to  one 
hundred  and  fifty  cubic  centimeters  of  chloroform  to 
extract  completely  the  blue  coloring  matter  which  has 
already  been  described.  The  quantity  of  coloring  mat- 
ter present  is  sufficient  to  impart  a  deep  blue  color  to 
this  volume  of  chloroform.  Ten  cubic  centimeters  of 
this  solution  are  placed  in  the  receptacle  of  the  Duboscq 
colorimeter  and  used  as  a  standard  for  comparison  with 
the  chloroform  color  solution  obtained  from  the  distil- 
late to  be  tested.  The  matching  of  the  colors  can 
usually  be  made  very  closely.  In  cases  where  the 
quantity  of  skatol  is  so  small  that  the  trace  of  indol 
present  influences  the  color  of  the  chloroform  solution, 
changing  it  to  violet  or  even  purple,  it  is  more  difficult 
to  obtain  a  satisfactory  matching  of  colors.  In  this 
case  is  may  be  necessary  to  add  a  small  quantity  of  indol 


144      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

to  the  skatol  employed  in  making  the  standard  color 
solution.  This  then  imparts  to  the  standard  color  solu- 
tion a  violet  tint  like  that  obtained  from  the  distillate 
to  be  matched.  It  seems  unnecessary  to  give  further 
details.  After  some  experience  with  the  method  of  match- 
ing colors  it  is  possible  to  employ  the  method  so  that  it 
will  give  satisfactory  quantitative  results. 

It  is  not  desirable  here  to  enter  into  a  description  of 
the  chemical  methods  of  studying  the  f  seces  and  the  urine. 
The  methods  ordinarily  employed  for  this  purpose  are 
fully  described  in  text-books  relating  to  these  subjects. 
It  may  be  stated,  however,  that  numerous  observations 
have  been  made  upon  the  acids  and  bases  present  in 
human  fseces  in  health  and  disease  and  the  intestinal 
contents  have  been  studied  for  hydrogen  sulphide  and  for 
the  presence  of  mercaptan.  The  reaction  of  the  fseces 
with  concentrated  solution  of  mercuric  chloride,  accord- 
ing to  the  manner  first  described  by  Schmidt,1  is  of  much 
value  in  determining  the  presence  of  a  substance  sup- 
posed to  be  hydrobilirubin.  The  marked  red  color 
with  yellowish  fluorescence  which  is  a  characteristic  of 
Schmidt's  reaction  is  supposed  to  depend  on  the  oc- 
currence of  a  combination  between  the  mercuric  salt 
and  hydrobilirubin.  An  analogous  combination  exists 
in  Jaffe's  zinc-chloride-urobilin  compound.  Both  sub- 
stances give  the  same  spectroscopic  picture;  namely, 
a  band  between  the  lines  b  and  E.  An  intensification 
of  the  red  color  obtained  in  the  Schmidt  reaction  may 
often  be  secured  by  transferring  a  portion  of  the  tested 

1  "  Verhandl.  d.  Congresses  f .  inn.  Medicin,"  xiii,  p.  320,  1895. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      145 

material  to  a  beaker  of  distilled  water.  Under  these 
circumstances  the  color  compound  diffuses  out  into  the 
water  and  imparts  to  it  a  distinct  and  often  strong  red 
color  which  is  frequently  more  pronounced  than  one 
would  have  predicted  from  the  appearance  of  the  mate- 
rial which  has  developed  the  red  color  under  the  influ- 
ence of  the  Schmidt  procedure  as  ordinarily  carried  out. 

In  the  course  of  a  systematic  examination  of  the  faeces 
from  normal  individuals  and  from  many  pathological 
series  it  was  noted  that  the  mercuric  chloride  reaction 
was  strongest  in  persons  suffering  from  intestinal  dis- 
orders, especially  in  those  with  intestinal  putrefaction. 
The  weakest  reactions  were  found  in  the  case  of  alcoholic 
stools  and  in  those  of  children  and  young  adults  present- 
ing only  slight  indications  of  intestinal  putrefactive 
decomposition  (low  ethereal  sulphates,  absence  of  indican, 
and  low  phenol). 

The  Dimethylamidobenzaldehyde  Reaction  of  the  Fceces. 
-  If  one  extracts  human  faeces  with  an  aqueous  sodium 
chloride  solution  (two  grams  of  fseces  to  twenty  grams 
of  0.85  per  cent,  sodium  chloride  solution),  the  extract 
will  usually  yield  a  color  reaction  with  a  suitably 
prepared  acid  solution  of  Ehrlich's  aldehyde.1  In  the 
case  of  healthy  children  or  adolescents  on  a  mixed  diet 
the  color  obtained  is  usually  a  light  rose,  and  may  be  very 
faint.  Between  this  light  tint  and  a  very  deep  cherry- 
red,  all  transitions  are  met.2 

1  Water,  270  c.c.;  concentrated  H2S04,  30  c.c.;  Ehrlich's  alde- 
hyde, 15  grams. 

2  We  have  employed  a  graded  color  scale  in  order  to  record  our 
results  with  some  degree  of  accuracy. 


146      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

The  explanation  of  the  chemical  basis  of  the  Ehrlich 
aldehyde  reaction  of  the  faeces  is  not  yet  wholly  sat- 
isfactory. Baumstark l  thought  it  could  be  ascribed 
to  the  indol  of  the  faeces  and  based  a  quantitative 
method  for  indol  on  the  reaction.  Bauer,2  however, 
showed  that  the  faeces  contain  another  substance  which 
reacts  with  the  aldehyde,  and  claims  that  this  substance 
is  urobilinogen.  I  reached  a  similar  conclusion  inde- 
pendently, after  noticing  that  the  faeces  in  one  instance 
gave  an  intense  red  reaction  after  the  indol  had  been 
distilled  off.  In  other  cases  a  strong  reaction  was  ob- 
tained in  spite  of  the  fact  that  the  faeces  were  free  from 
indol  from  the  outset.  That  the  reaction  from  this  non- 
volatile part  of  the  faeces  depends  wholly  on  urobilino- 
gen does  not  appear  to  me  to  have  been  convincingly 
shown.  It  is  true,  however,  that  one  may  reduce 
urobilin  (Schuchardt's)  with  alkali  and  zinc  dust  and 
thus  obtain  a  substance  which  gives  a  stronger  and 
more  characteristic  Erhlich  aldehyde  reaction  than 
the  urobilin  itself.  Probably  both  urobilinogen  and 
a  skatol  derivative  are  implicated  in  the  Ehrlich 

1  "  Bestimmungen  der  Faulniss  Produkte  im  Urin  und  in  dem 
Faces     mit     Beniitzung    der    Ehrlichschen     Aldehydreaktion," 
Munch,   med.   Wochenschr.,  1,  p.   722,   1903;    also  Arch.  f.  Ver- 
dauungskrankh.,  ix,  p.  201,  1903. 

2  This  distillation  should  be  conducted  in  an  atmosphere  of 
carbon  dioxide  in  order  to  prevent  oxidation  of  the  reacting  sub- 
stance, which  is  sensitive  both  to  air  and  to  the  action  of  sunlight. 

Bauer  fell  into  error  in  claiming  that  the  reaction  from  the 
faeces  is  not  due  to  indol  and  that  the  method  does  not  serve 
for  the  detection  of  this  substance.  I  am  confirmed  in  this 
view  by  Ury  ("Die  Ehrlich'sche  Reaction  im  Stuhl,"  Zentralbl. 
f.  innere  Medizin,  xxvii,  p.  41,  1906). 


INFECTIONS  OF  THE  DIGESTIVE  TRACT       147 

aldehyde  reaction  of  the  urine,  but  it  is  possible  that 
other  substances  are  also  concerned. 

The  relation  of  the  hydrobilirubin  reaction  to  the 
urobilinogen  reaction  of  the  faeces  with  Ehrlich's 
aldehyde  is  a  point  of  interest  on  which  one  cannot 
at  present  express  an  opinion.  There  are  instances  in 
which  the  faeces,  after  distillation  of  all  the  indol  pres- 
ent (as  shown  by  the  aldehyde  reaction,  which  is  very 
delicate),  still  give  a  reaction  in  the  cold  with  a  di- 
me thylamidobenzaldehyde  solution.  This  reaction  is 
believed  to  depend  on  the  presence  of  urobilinogen.  It 
has  been  fairly  well  marked  in  some  of  our  anaemia 
cases,  but  there  is  as  yet  no  evidence  that  the  reaction 
bears  any  definite  relation  to  the  hydrobilirubin 
reaction,  although  the  two  substances  urobilinogen  and 
urobilin  (hydrobilirubin  ?)  are  closely  related  chemically. 

The  Dimethylamidobenzaldehyde  Reaction  of  the  Urine. 
—  It  is  well  known  that  on  the  addition  of  acid 
solution  of  dimethylamidobenzaldehyde  to  certain 
urines  a  red  color  is  obtained,  sometimes  in  the  cold, 
more  often  only  on  the  addition  of  heat.  The  explana- 
tion of  the  reaction  has  been  the  occasion  of  considerable 
discussion.  Ehrlich  *  was  inclined  to  attribute  it  to 
glycosamin;  Neubauer2  and  Bauer3  referred  it  to 

1"Ueber  die  Dimethylamidobenzaldehydreaction,"  Med. 
Woche,  p.  151,  1901. 

2  "  Ueber  die  neue  Ehrlich'sche  Reaction  mit  Dimethylamido- 
benzaldehyd,"  Sitzungsber.  d.  Gesellsch.  /.  Morphol.  u.  Physiol.,  ii, 
p. 32, 1903. 

3  "Die   Ehrlich'sche   Aldehydreaktion  im   Harn  und   Stuhl," 
Zentralbl.  f.  inn.  Med.,  xxvi,  p.  833,  1905. 


148      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

urobilogen,  which  has  passed  from  the  intestine  into  the 
urine.  I  have  found  that  the  administration  of  skatol 
to  men  and  to  monkeys  is  followed  by  some  intensifica- 
tion of  the  Ehrlich  aldehyde  reaction,  and  believe  that 
where  skatol  is  produced  in  the  intestine  it  may  con- 
tribute to  intensify  the  reaction.1  Dr.  Adolf  Meyer, 
Director  of  the  Pathological  Institute  of  the  State 
Hospitals  for  the  Insane,  tells  me  that  in  some  observa- 
tions made  under  his  direction  the  administration  of 
skatol  to  patients  has  been  followed  by  a  similar  though 
slight  intensification  of  the  dimethylamidobenzaldehyde 
reaction  of  the  urine. 

This  reaction  is  seldom  found  in  its  most  intense  form 
except  in  the  urines  from  persons  suffering  from  patho- 
logical conditions.  It  was  noticed  by  Ehrlich  that  the 
intensity  of  the  reaction  is  apt  to  be  great  in  the  case 
of  patients  with  phthisis,  typhoid  fever,  and  chronic 
enteritis,  and  Clemens  observed  that  persons  with  digest- 
ive disorders  are  among  those  whose  urines  are  likely 
to  give  a  strong  reaction.  It  has  appeared  to  me  that 
the  urines  of  persons  with  the  urinary  evidences  of  exces- 
sive chronic  intestinal  putrefaction  (excessive  indican  and 
phenol  and  high  ethereal  sulphates)  are  especially  liable 
to  exhibit  the  deepest  cherry-color  tints  on  being  treated 
with  the  reagent.  The  urine  of  normal  children,  in 
whom  the  processes  of  intestinal  putrefaction  are  apt 
to  be  mild,  usually  give  negative  or  almost  negative 

1 "  On  a  Relation  between  Skatol  and  he  Dimethylamidobenz- 
aldehyde Reaction  of  the  Urine,"  Journ.  Biol.  Chem.,  i,  p.  251, 
1905. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT       149 

results.  Although  I  have  come  to  associate  an  intense 
Ehrlich  aldehyde  reaction  of  the  urine  with  the  occurrence 
of  a  high  degree  of  intestinal  putrefaction,  it  must  be 
admitted  that  not  every  case  of  excessive  intestinal 
putrefaction  shows  this  reaction  in  its  very  marked 
form.1 

1  A  good  discussion  of  Ehrlich's  dimethylamidobenzaldehyde 
reaction  in  the  urine  by  C.  E.  Simon  may  be  found  in  the  American 
Journal  of  the  Medical  Sciences,  cxxvi,  p.  471,  1903.  Bauer  (loc. 
tit.)  brings  forward  evidence  to  support  the  view  that  the  Ehrlich 
reaction  depends  on  urobilinogen.  This  view  appears  to  me  not 
irreconcilable  with  the  fact  that  the  administration  of  skatol 
intensifies  or  even  gives  rise  to  this  reaction,  since  more  than  one 
factor  may  be  operative  in  certain  instances.  I  am  not  certain 
of  the  identity  of  the  reactions  obtained  by  Bauer  and  those 
dependent  on  the  administration  of  skatol,  as  I  have  failed  to 
make  use  of  spectroscopic  methods  of  study. 


COMMON  BACTERIAL  INFECTIONS  OF  THE  DI- 
GESTIVE TRACT,  CONSIDERED  FROM  THE 
STANDPOINT  OF  THE  MICROORGANISMS 

THE   COLON-TYPHOID-DYSENTERY   GROUP 

A  SURVEY  of  the  bacteria  which  we  may  include  in 
the  colon-typhoid-dysentery  group  is  beset  with  many 
difficulties  with  respect  to  satisfactory  classification, 
arising  from  an  incomplete  knowledge  of  the  biological 
characters  of  these  bacteria.  We  know  enough,  however, 
to  see  that  we  are  dealing  with  microorganisms  not  sep- 
arated from  one  another  by  unbridged  gaps,  but  rather 
linked  in  series  by  most  intimate  affinities. 

Colon  Bacilli.  —  If  we  ask  the  question,  what  patho- 
logical consequences  do  the  colon  bacilli  of  the  human 
intestine  bring  to  the  human  species,  the  answer  is 
by  no  means  simple.  Many  conditions  formerly  at- 
tributed to  the  colon  bacilli  were  given  their  position 
without  adequate  reason.  To-day  we  have  the  right  to 
insist  on  knowing  the  fermentative  and  agglutinative 
as  well  as  the  cultural  characters  of  the  colon  organisms 
which  are  stated  to  be  the  causes  of  disease,  and  too 
often  this  information  is  not  given. 

At  the  present  time  the  view  is  generally  held  by 
pathologists  that  colon  bacilli  are  capable  of  doing 
damage  in  two  ways,  as  infective  agents  outside  the 

150 


INFECTIONS  OF  THE  DIGESTIVE  TRACT       151 

digestive  tract  and  as  infective  agents  inside  the  tract. 
We  are  not  concerned  here  with  those  examples  of  colon- 
bacillus  infection  in  which  the  organisms  find  their  way 
into  the  urinary  tract  from  the  exterior  and  set  up  a 
cystitis  or  pyelitis.  Nor  shall  I  do  more  than  refer  to 
those  infections  in  which  colon  bacilli  have  passed  during 
life  through  some  local  spot  of  injury  in  the  digestive 
tract  into  the  blood  or  the  peritoneal  cavity,  setting  up 
in  the  former  case  a  septicaemia  or  pyaemia,  and  in  the 
latter  a  peritonitis.  With  less  serious  consequences 
than  these,  the  colon  organisms  probably  often  pass 
temporarily  from  the  digestive  tract  by  way  of  the  blood, 
to  the  kidney,  with  a  resulting  pyelonephritis  or  pyelitis, 
or  at  least  a  bacteriuria.  It  is  noteworthy  that  the 
localization  of  colon  bacilli  under  such  pathological 
conditions  as  these  is  often  attended  by  a  heightened 
virulence  for  small  animals  as  compared  with  the  vir- 
ulence of  the  original  bacteria  of  the  intestine. 

The  question  which  does  especially  interest  us  here  is 
whether  the  colon  bacilli  of  an  individual  ever  do  injury 
to  that  individual  while  still  confined  to  the  digestive 
tract.  In  attempting  to  answer  it,  I  must  divide  the 
question  into  two  —  one  relating  to  acute  effects  of  the 
colon  bacilli,  the  other  relating  to  prolonged  pathological 
activities. 

If  we  go  back  to  the  time  when  Escherich  first  de- 
scribed B.  coli  commune  as  an  obligate  inhabitant  of  the 
human  digestive  tract,  we  find  that  there  was  a  dis- 
position to  regard  it  as  the  cause  of  various  diarrhreal 
affections.  A  close  examination  of  facts  relating  to  the 


152      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

identity  of  the  organisms  in  many  instances  makes  it 
clear  that  affections  attributed  to  colon  bacilli  were  thus 
classed  without  sufficient  justification.  For  example, 
many  instances  of  supposedly  colon-bacillus  diarrhoea 
must  almost  certainly  have  been  due  to  the  dysentery 
bacillus.  Remembering  the  cultural  similarities  of  certain 
colon  bacilli  and  dysentery  bacilli,  it  is  easy  to  under- 
stand how  confusion  might  have  occurred  when  the 
fermentative  characters  were  left  out  of  account,  as 
was  usually  the  case.  Even  an  organism  so  different 
from  B.  coli  as  the  bacillus  of  typhoid  fever  was  con- 
founded with  it  in  the  early  days  of  bacteriology,  when 
limited  cultural  criteria  alone  were  employed.  Thus 
progress  in  methods  of  identification  has  step  by  step 
circumscribed  the  conception  of  the  colon  bacillus  and 
given  it  sharper  definition.  There  are  indications  that 
this  process  of  circumscription  has  not  reached  its  final 
stage. 

It  seems  established  that  organisms  having  the  cultural 
fermentative  and  agglutinative  characters  of  B.  coli  at 
times  are  endowed  with  a  degree  of  virulence  for  small 
animals  which  does  not  pertain  to  colon  bacilli  derived 
from  healthy  human  individuals.  Such  pathogenic 
bacilli  have  been  found  in  great  abundance  in  some 
diarrhceal  conditions  and  appear  to  have  been  the  cause 
of  these  acute  derangements.  It  is  not  clear  whether 
in  such  cases  the  dominant  normal  organisms  have 
acquired  increased  irritant  properties  or  whether  there 
has  occurred  a  process  of  substitution  by  which  organisms 
present  normally  in  small  numbers  or  introduced  from 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      153 

outside  temporarily  gain  the  numerical  ascendency  in 
consequence  of  alterations  in  the  nutrient  media  which 
favor  this  race  while  repressing  the  ordinary  dominant 
one.  In  addition  to  a  colon-bacillus  diarrhoea  associated 
with  colon  bacilli  of  more  than  ordinary  virulence,  it  is 
probable  that  we  must  recognize  a  similar  derangement 
in  which  there  is  no  increase  of  virulence  on  the  part  of 
the  bacilli,  but  simply  an  enormous  physiological  increase 
which  verges  on  the  pathological.  Almost  any  healthy 
child  who  has  eaten  a  largely  excessive  quantity  of 
ripe  fruit,  rich  in  sugar,  will  develop  loose  movements  in 
which  colon  bacilli  are  present  in  very  large  numbers.  I 
do  not  know  whether  these  organisms  are  any  more  viru- 
lent than  the  type  dominant  previous  to  the  excessive 
indulgence,  but  it  seems  extremely  unlikely  that  they 
suffer  any  appreciable  change  in  the  course  of  the  short 
interval  of  excessive  fermentative  activity.  Acetic, 
lactic,  and  other  organic  acids  are  formed  in  the  course 
of  the  fermentative  process  rendered  possible  by  the 
sugar-holding  fruit,  and  it  is  to  the  irritant  action  of 
these  acids,  and  perhaps  also  to  an  excessive  liberation 
of  gas,  that  the  symptoms  must  be  ascribed.  Very 
likely,  too,  in  a  case  like  this,  bacilli  of  the  group  of  B. 
lactis  aerogenes  aid  in  the  fermentation.  In  this  instance 
we  are  dealing  clearly  with  a  process  on  the  borderland 
between  the  physiological  and  the  pathological. 

Of  the  influence  exerted  by  colon  bacilli  in  the  course  of 
chronic  processes  within  the  digestive  tract  we  have  as 
yet  little  knowledge,  partly  because  etiological  relations 
are  very  difficult  to  establish  in  the  case  of  obligate 


154      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

bacteria.  Attention  has  lately  been  called  by  Dr. 
Turck  *  of  Chicago  to  the  fact  that  he  has  experimentally 
induced  in  dogs  the  formation  of  ulcers  of  the  stomach 
in  many  respects  comparable  to  those  occurring  in  man. 
The  fact  is  in  itself  one  of  considerable  interest  to  pathol- 
ogists,  although  its  bearing  on  the  etiology  of  human 
gastric  ulcers  is  obscure.  The  reported  experimental  re- 
sults were  obtained  by  feeding  dogs,  during  considerable 
periods,  bouillon  cultures  of  bacilli  derived  from  patients 
with  gastric  ulcer.  The  bacilli  are  stated  to  have  been 
colon  bacilli,  but  it  is  regretable  that  the  cultural  and 
biochemical  characters  of  the  bacteria  are  not  mentioned. 
Moreover,  while  it  seems  likely  that  human  colon  bacilli 
may  in  disease  migrate  to  the  gastric  region  and  multi- 
ply freely  there,  this  is  not  now  known  to  be  the  case  in 
ulcer.2 

In  considering  the  part  played  by  the  colon  bacilli  in 
chronic  disorders  one  fact  stands  out  distinctly  and  gives 
us  a  clew  to  the  nature  of  the  activity  of  these  bacilli. 
Human  colon  bacilli  have  practically  no  power  to  dis- 
solve and  peptonize  native  proteids,  such  as  casein  or 
egg  albumen.  I  conclude  from  experiments  which  I 

J" Ulcer  of  the  Stomach;  Pathogenesis,  Pathology,"  Journ. 
Amer,  Med.  Assoc.,  xlvi,  p.  1753,  1906. 

2  The  association  of  colon-bacillus  infection  of  the  stomach  with 
gastric  ulcer  would  not  of  course  prove  an  etiological  relation,  as 
the  infection  might  be  a  secondary  phenomenon.  Moreover,  it 
must  be  remembered  that  the  production  of  ulcers  in  dogs  by  means 
of  human  colon  bacilli  involves  the  action  of  foreign  organisms. 
The  presence  of  the  obligate  and  homologous  colon  bacilli  of  man 
in  the  human  stomach  is  thus  not  strictly  comparable  with  the 
conditions  induced  in  Turck's  experiments. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      155 

have  made  on  milk  that  the  peptonizing  action  of  these 
bacilli  is  extremely  slight,  though  not  absolutely  lacking. 
On  the  other  hand,  the  colon  bacilli  are  able  to  cleave 
energetically  peptones  prepared  by  other  microorgan- 
isms. Then  they  give  rise  to  familiar  products  of  pu- 
trefaction such  as  ammonia,  volatile  fatty  acids,  phenol 
and  indol,  and  hydrogen  sulphide.  These  facts  have  an 
important  bearing  on  the  significance  of  these  bacteria 
within  the  digestive  tract,  which  may  be  summarized 
as  follows.  If  there  is  good  absorption  of  proteids  above 
the  lower  ileum,  that  is,  above  the  level  where  there  is 
a  predominance  of  colon  bacilli,  little  proteid  material 
finds  its  way  into  the  colon.  Hence  whatever  may  be  the 
nature  of  the  bacterial  inhabitants  of  the  large  intestine, 
but  little  putrefactive  decomposition  occurs  there.  But 
if,  owing  to  a  superabundance  of  proteid  food  consid- 
erable native  proteid  finds  its  way  into  the  colon,  its 
fate  depends  on  the  character  of  the  flora  there.  In  a 
normal  intestine,  containing  few  peptonizing  bacteria, 
there  will  be  little  putrefaction,  because  the  dominant 
races,  members  of  the  coli  group,  cannot  initiate  active 
putrefaction  of  native  proteids.  But  if  there  be  present 
also  putrefactive  anaerobes  capable  of  peptonizing  pro- 
teids, the  colon  bacilli  take  an  active  part  in  breaking 
down  the  hydrolyzed  proteids  with  which  they  are  thus 
supplied.  In  this  way  the  colon  bacilli  frequently  be- 
come active  participants  in  excessive  intestinal  putre- 
faction. I  shall  recur  to  this  subject  in  the  discussion 
of  the  putrefactive  anaerobes. 
The  disappearance  of  typical  colon  bacilli  from  the 


156      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

fasces  of  persons  in  whom  such  bacteria  have  previously 
been  present  is  a  phenomenon  of  much  interest.  It  is 
observed  in  a  variety  of  pathological  conditions :  in  cases 
of  excessive  saccharo-butyric  putrefaction  due  to  infec- 
tion with  B.  aerogenes  capsulatus,  in  some  cases  of 
mucous  colitis,  in  certain  instances  of  dysentery  due  to 
the  Shiga  bacillus.  Probably  it  occurs  also  in  cholera 
and  typhoid  fever. 

The  disappearance  of  B.  coli  from  the  contents  of  the 
lower  bowel  is  in  itself  no  proof  that  these  organisms 
are  not  present  higher  up,  but  I  think  it  presumptive 
evidence  that  the  growth  of  these  obligate  bacteria  is  at 
least  more  restricted  at  higher  levels  than  is  normally 
the  case.  Frequently  the  failure  to  find  living  colon 
bacilli  in  the  faeces  is  representative  of  the  entire  gastro- 
enteric  tract,  since  in  these  cases  diarrhceal  movements 
(spontaneous  or  due  to  purgatives)  also  fail  to  contain 
them. 

One  is  justified  in  suspecting  a  complete  or  partial 
suppression  of  B.  coli  if  the  mixed  faecal  flora  fails  to 
form  gas  in  sugar-bouillon  fermentation  tubes  or  makes 
gas  in  smaller  quantities  than  is  usual  for  normal  flora. 
This  suspicion,  if  correct,  is  confirmed  by  the  failure  of 
colon  bacilli  to  appear  on  litmus  gelatin  plates  or  by 
their  appearance  in  abnormally  small  numbers. 

The  possibility  that  some  cases  of  mucous  colitis  are 
due  to  colon  bacillus  infection  has  been  suggested  by 
Sir  A.  E.  Wright,  who  tells  me  that  he  has  cured  certain 
obstinate  and  extreme  instances  of  this  affection  by 
inoculations  made  with  killed  colon  bacilli.  The  bacilli 


INFECTIONS  OF  THE  DIGESTIVE  TRACT       157 

used  for  inoculation  were  obtained  in  one  instance  from 
the  cystitic  urine  of  the  patient.  The  study  of  mucous 
colitis  from  this  standpoint  appears  promising.  It  is 
very  desirable  that  the  biochemical  characters  of  the 
bacilli  concerned  in  this  disease  should  be  well  established. 
The  possibility  has  not  been  excluded,  I  think,  that  in 
the  cases  mentioned  by  Dr.  Wright  the  organisms  con- 
cerned were  not  typical  colon  bacilli,  but  closely  related 
pathological  varieties. 

Typhoid  Bacilli.  — It  has  just  been  pointed  out  that 
organisms  of  the  strict  colon  bacillus  group  are  not  at 
present  known  to  be  the  cause  of  severe  acute  intestinal 
diseases  and  that  their  chief  role  in  chronic  disorders 
of  the  intestine  depends  on  their  participating  in  putre- 
factive decompositions.  We  may  briefly  consider  a 
microorganism  which,  while  closely  affiliated  to  the  colon 
bacillus,  is  morphologically  and  in  cultural  characters 
different  from  it  in  important  biochemical  properties 
and  is  immeasurably  more  pathogenic  for  the  human  race. 
This  is  the  bacillus  of  typhoid  fever  discovered  by  Eberth 
and  Gaffky  independently  in  1884.  This  organism  as 
compared  with  the  colon  bacillus  is  far  less  hardy  in  its 
growth  on  ordinary  culture  media  and  requires  much 
more  special  conditions  in  order  to  thrive  —  conditions 
which  it  often  finds  in  the  human  body.  We  do  not  know 
in  what  relation  it  stands  to  the  colon  bacillus  in  the  long 
process  of  natural  evolution.  The  claim  that  colon 
bacilli  can  be  experimentally  transformed  into  typhoid 
bacilli  has  never  been  made  good,  and  still  we  cannot 
deny  that  what  bacteriologists  cannot  do  in  the  laboratory 


158      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

may  possibly  have  been  done  by  nature  and  may 
perhaps  be  still  in  progress.  The  existence  of  bacteria 
intermediate  between  colon  bacilli  and  typhoid  bacilli  - 
the  paratyphoid  and  paracolon  bacteria  —  is  now  es- 
tablished, and  the  fact  that  there  are  these  transitional 
forms  suggests  that  they  may  have  been  descended 
from  a  common  ancestor  through  successive  slow  modi- 
fications.1 

1  The  studies  of  Doebert  ("Die  verwandtschaftlichen  Bezie- 
hungen  zwischen  den  Bacillus  faecalis  alkaligenes  und  dem  Ty- 
phusbazillus,"  Archiv  f.  Hyg.,  lii,  p.  70,  1905)  indicate  that 
there  exists  a  close  resemblance  between  the  bacillus  of  typhoid 
fever  and  Petruschky's  B.  fcBcalis  alcaligenes.  A  culture  of  the 
latter  organism  furnished  by  Petruschky  rendered  litmus  milk 
blue  in  twenty-four  hours,  forming  a  pellicle  on  the  surface  of  the 
milk,  and  on  potato  gave  a  yellowish  brown  growth  in  one  day. 
With  typhoid  serum  the  organism  agglutinated  in  1 : 800.  It  is 
stated  that  it  was  easy  to  modify  the  organism  of  Petruschky  by 
passing  it  through  guinea-pigs  so  that  it  acquired  the  cultural 
characters  of  the  true  typhoid  bacilli.  The  organism  modified  by 
Doebert  experimentally  by  passage  through  guinea-pigs  was  not 
agglutinated  by  the  serum  from  guinea-pigs  in  1 :  100,  but  was 
agglutinated  by  typhoid  serum  in  a  dilution  of  1 : 15,000.  An- 
other strain  of  B.  fcecalis  alcaligenes  studied  by  Doebert  could  not 
be  converted  in  this  manner  into  an  organism  so  closely  resembling 
the  typhoid  bacillus  by  means  of  passage  through  animals. 

There  appears  to  be  little  doubt  that  B.  fcecalis  alcaligenes  is 
sometimes  responsible  for  the  occurrence  of  a  febrile  disease  at 
present  indistinguishable  from  mild  forms  of  typhoid  fever  on 
purely  clinical  grounds.  Though  closely  related  to  the  bacillus 
of  typhoid  fever,  it  appears  proper  to  regard  the  bacillus  of  Pe- 
truschky as  a  distinct  bacterium.  (For  details  as  to  the  distinction 
of  B.  fcecalis  alcaligenes  and  B,  typhi  see  Piorkowski,  "Zur  Differ- 
enzierung  der  Typhusbacillus  und  Bacillus  fsecalis  alkaligenes," 
CentralbL  /.  Bakt.,  I  Abt.,  Orig.,  xl,  p.  437,  1905-06.)  It  seems 
most  reasonable  to  look  upon  B.  fcecalis  alcaligenes  as  a  variant  of 
the  typhoid  bacillus  which  has  lest  the  capacity  to  act  fermenta- 
tively  on  dextrose.  Something  might  be  said  in  favor  of  regarding 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      159 

While  colon  bacilli  possess  in  a  marked  degree  certain 
commonplace  properties  such  as  the  ability  to  coagulate 
milk,  to  reduce  neutral  red,  to  make  indol,  and  to  ferment 
sugars,  with  the  liberation  of  gas  and  acids,  these  prop- 
erties have  been  lost  in  the  case  of  the  typhoid  bacilli, 
excepting  only  the  capacity  to  form  acid  from  sugars. 
In  respect  to  these  characters,  the  paracolon  and  para- 
typhoid bacilli  occupy  an  intermediate  position.  The 
loss  of  these  relatively  banal  properties  has  been  asso- 
ciated with  the  development  of  pathogenic  properties 
for  man  —  properties  which  are  doubtless  dependent 
on  substances  chemically  well  defined  but  at  present 
quite  unknown.  It  has,  for  several  years,  been  recog- 
nized by  students  of  immunity  that  in  respect  to  the 
formation  of  these  toxic  substances  there  is  a  striking 
inconsistency  in  the  behavior  of  the  typhoid  bacilli 
in  the  body  and  in  artificial  culture  media;  for  in  the 
former  case,  while  they  make  poisons  oftefi  sufficiently 
active  to  kill,  in  the  latter  only  feeble  poisons  are  obtain- 
able. In  partial  explanation  of  this  the  view  was  ad- 
vanced that,  unlike  the  bacilli  of  diphtheria,  which  make 

it  as  a  hog-cholera  variant  or  even  as  an  extreme  modification  of 
B.  coli.  Its  active  motility,  however,  places  it  nearest  to  the 
typhoid  or  paratyphoid  groups.  Brion  and  Kayser  ("Die  nosolo- 
gische  Stellung  des  Symptomkomplexes  'Abdominaltyphus,'" 
Deutsches  Archiv  /.  klin.  Med.,  Ixxxv,  p.  552,  1905-06)  have  de- 
scribed an  organism  differing  distinctly  from  typhoid  bacillus, 
but  which  was  obtained  from  a  patient  showing  a  fever  clinically 
resembling  a  mild  typhoid.  From  the  blood  of  this  patient  an 
organism  was  cultivated  which  agglutinated  with  the  patient's 
serum  in  a  dilution  of  1 :  500.  It  had  the  property  of  liquefying 
gelatin  and  formed  yellow  colonies.  They  gave  to  it  the  name 
of  Bacterium  flavosepticum. 


160      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

soluble  poisons  diffusing  readily  from  the  bodies  of  the 
bacteria,  the  typhoid  bacilli  hold  their  poisons  tena- 
ciously in  their  bodies,  and  that  these  endotoxins  may 
be  liberated  in  the  body  of  the  host,  when  the  bacterial 
bodies  are  dissolved,  but  are  not  so  liberated  in  ordinary 
culture  media.  A  more  adequate  hypothesis  was  formu- 
lated by  Professor  Welch.  According  to  this,  the  typhoid 
bacilli  are  stimulated  in  the  body  by  means  of  its  defen- 
sive juices  to  form  and  liberate  their  poisons.  Such  a 
stimulus  being  wholly  lacking  in  artificial  culture  media, 
where  their  existence  is  not  actively  threatened,  the 
bacilli  are  not  forced  to  make  their  poisons.  It  may  be 
that  the  difference  in  the  poisons  formed  in  the  body 
and  in  culture  media  is  mainly  one  of  quantity  rather 
than  of  kind.  There  is  at  least  some  ground  for  think- 
ing that  the  character  of  the  immunity  is  the  same, 
whether  the  poison  comes  from  the  bodies  of  bacteria 
in  culture  or  from  similar  bacteria  under  the  stimulus 
of  the  protective  juices  of  an  animal. 

The  word  "aggressins"  has  been  introduced  by  Kruse 
and  Oscar  Bail 1  to  designate  substances  of  unknown 
constitution  which  are  formed  by  most  pathogenic 
bacteria  when  in  antagonism  with  the  animal  organism, 
as  for  example  when  introduced  into  the  peritoneal 
cavity  of  a  guinea-pig  —  substances  which  break  down  in 
some  way  the  natural  defenses  of  the  body,  so  that  the 
bacterial  invaders,  previously  held  in  check,  become 
reproductively  and  invasively  active.  The  "aggressins" 

1 "  Untersuchungen  liber  Typhus  und  Cholera  Immunitat," 
Archiv  /.  Hyg.,  lii,  p.  272,  1905. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      161 

were  obtained  from  the  peritoneal  exudate  and  carefully 
separated  from  cellular  elements  by  the  centrifuge. 
It  was  found  that  numbers  of  typhoid  or  cholera  bacilli 
below  the  fatal  dose  become  fatal  when  injected  simul- 
taneously with  "aggressins,"  that  it  is  possible  by  means 
of  "aggressins"  to  inhibit  the  protective  action  of  a 
bacterial  immune  serum  in  the  peritoneal  cavity  of  the 
guinea-pig,  and,  finally,  that  one  may  by  suitable  treat- 
ment with  "aggressins"  induce  immunity  to  fatal 
doses  of  typhoid  or  cholera  bacilli.  Bail  regards  this 
"aggressin"  immunity  as  something  distinct  from  a 
bactericidal  immunity  because  a  bacterial  immune  serum 
does  not  protect  against  "aggressins,"  but  very  recent 
studies  by  Wassermann  and  Citron 1  indicate  that 
"aggressins"  are  really  bacterial  extracts,  and  that  their 
influence  in  promoting  infection  depends  on  their  ability 
to  bind  defensive  substances  largely  derived  from  leu- 
cocytes and  designated  complements  in  Ehrlich's  ter- 
minology. It  is  not  yet  clear  whether  the  "aggressins" 
really  act  through  binding  complements  in  vivo  or  not, 
and  this  is  a  crucial  point.2  Hence  we  cannot  feel  certain 
how  to  interpret  Sir  A.  E.  Wright's  observations  on  the 
immunization  of  English  soldiers  against  typhoid  fever, 
in  which  he  met  with  at  least  a  measure  of  success  by 

1  Wassermann   and  Citron,   "  Ueber   die   Bildungsstatten  der 
Typhusimmunkorper,"  Zeitschr.  f.  Hyg.,  1,  p.  331,  1905;  Citron, 
"Ueber    nattirliche    und    kiinstliche    Aggressine,"     Centralbl.    f. 
Bakt.,  I  Abt.,  Orig.,  xli,  p.  230,  1906;  "Die  Immunisierung  gegen 
die  Bakterien  der  Hogcholera  (Schweinpest)  mit  Hilfe  von  Bak- 
terienextrakten,"  Zeitschr.  f.  Hyg.,  liii,  p.  515,  1906. 

2  Wolff-Eisner,  "Die  Aggressinlehre,"  Centralbl.  f.  Bakt.,  I  Abt., 
Ref .,  xxxviii,  p.  641,  1906. 

K 


162      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

vaccinating  with  typhoid  bacilli  killed  by  heating  to 
60°  to  65°  C. —  a  procedure  which  he  dared  to  practice 
after  learning  from  Pfeiffer  that  he  had  in  man  obtained 
the  specific  agglutination  reaction  of  typhoid  fever  after 
the  subcutaneous  inoculation  of  a  heated  culture  of 
typhoid  bacilli.  Chantemesse  in  1904  obtained  ap- 
parently favorable  results  in  the  treatment  of  typhoid 
fever  by  the  use  of  a  serum  that  developed  in  horses 
treated  with  a  filtrate  from  typhoid  bacilli  which  had 
grown  on  a  medium  containing  splenic  pulp  and  human 
defibrinated  blood.  It  is  possible  that  this  serum  acts 
by  binding  the  "aggressins"  made  by  the  typhoid  bacilli 
as  they  grow,  thus  removing  in  some  degree  a  condition 
favorable  for  the  multiplication  of  the  typhoid  bacilli. 

We  may  conveniently  classify  bacteria  in  a  rough 
way  according  to  the  degree  of  parasitism  they  exhibit. 
Thus  the  plague  bacillus  in  man  and  the  anthrax  bacillus 
in  guinea-pigs  are  highly  parasitic,  for  they  find  in  their 
hosts  the  conditions  that  permit  their  rapid  multiplica- 
tion and  invasion,  although  the  original  infection  may 
have  been  established  by  very  few  bacteria,  perhaps  even 
by  a  single  bacterium.  Directly  opposed  to  the  parasites 
stand  the  saprophytic  bacteria,  which  have  the  utmost 
difficulty  in  multiplying  in  the  tissues  of  their  host 
even  when  introduced  in  large  numbers,  but  may  prove 
injurious  if  inoculated  in  enormous  quantities.  Many 
of  the  bacteria  of  the  intestinal  tract  are  of  this  character. 
Midway  between  these  groups  stand  the  hemiparasites, 
microorganisms  which  are  invasive  only  when  inoculated 
in  considerable  numbers  and  are  pathogenic  only  when 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      163 

the  way  has  been  prepared  by  poisons  which  neutralize 
the  defensive  substances  of  the  host;  for  example,  by 
"aggressins."  The  bacilli  of  typhoid  fever  and  of  cholera 
may  be  classed  as  hemiparasites,  and  their  virulence 
appears  to  stand  in  a  close  relation  to  the  efficiency  of 
their  "aggressins." 

The  ordinarily  accepted  view  that  the  portal  of  infec- 
tion for  the  inciters  of  typhoid  fever  is  the  digestive 
tract  is  doubtless  true  in  general  and  still  it  may  not 
represent  the  whole  truth.  There  is  some  evidence  to 
support  the  idea  that  at  times  the  bacilli  enter  by  way 
of  the  throat,  for  the  organisms  have  been  found  in  the 
tonsil,  and  a  patient  may  be  in  the  early  period  of  the 
disease  without  showing  the  presence  of  the  bacilli  in 
the  stools  even  when  modern  methods  of  isolation  are 
employed.  It  is  conceivable  that  typhoid  bacteria  in 
the  intestine  do  not  necessarily  point  to  an  original 
intestinal  invasion,  as  they  may  at  times  come  mainly 
from  ulcerated  Peyer's  patches  in  which  the  bacilli 
have  accumulated  as  a  result  of  the  invasion  of  these 
lymphatic  structures  in  the  course  of  a  general  bacillary 
infection  which  strongly  tends  to  implicate  the  lym- 
phatics. It  would  be  of  special  interest  to  know  whether 
the  axillary  and  other  lymph  nodes  at  a  distance  from 
the  intestine  are  early  invaded  in  typhoid  fever.  Even 
where  the  invasion  is  by  the  intestinal  path  the  typhoid 
bacilli,  which  tend  to  be  irregularly  distributed  in  the 
intestinal  contents,  may  perhaps  come  from  ulcerated 
Peyer's  patches  which  have  become  infiltrated  and  ulcer- 
ated, secondarily  to  the  typhoidal  bacilla3mia.  We  should 


164     INFECTIONS  OF  THE  DIGESTIVE  TRACT 

then  be  dealing  with  an  eliminative  process  for  bacteria, 
such  as  pharmacologists  have  long  known  to  exist  for 
poisons  like  carbolic  acid,  corrosive  sublimate,  and  urea, 
and  such  as  Dr.  Flexner  has  shown  to  exist  for  ricin 
poisoning  and  for  intoxications  arising  from  the  auto- 
lyzed  dysentery  poison. 

That  the  blood  contains  typhoid  bacilli  early  in  the 
course  of  the  fever  is  now  well  established  for  a  very 
large  proportion  of  all  cases  appropriately  examined,  and 
is  probably  true  of  all  cases  of  typhoidal  type  associated 
with  infection  by  typhoid  bacilli.  This  bacillsemia 
explains  many  of  the  complications  and  sequelae  of  the 
disease,  the  passage  of  bacilli  into  the  spleen  with  en- 
largement of  the  organ,  their  passage  into  the  liver  and 
hence  into  the  gall-bladder  (frequently  with  cholecystitis, 
with  or  without  gall-stone  formation)  and  the  entry 
of  the  bacilli  into  the  urine,  where  they  may  be  found 
for  some  weeks  after  the  subsidence  of  the  fever.  That 
these  living  bacilli  should  find  their  way  abundantly 
into  the  urine  after  convalescence  has  begun  shows  that 
the  microorganisms  must  still  have  a  foothold  in  the 
host,  and  points  to  unnumbered  possibilities  in  respect  to 
relapses  and  the  spread  of  the  bacilli.  It  could  hardly 
have  been  predicted  that  convalescence  is  possible 
while  the  living  inciters  of  the  disease  still  persist  in  the 
body  of  the  host.  The  explanation  of  this  apparent 
paradox  must  be  sought  in  the  development  of  protective 
powers  on  the  part  of  the  host,  powers  which  accrue  to 
the  host  in  consequence  of  the  specific  excitation  and 
reaction  of  many  different  types  of  cells  through  sub- 


INFECTIONS  OF  THE  DIGESTIVE  TRACT       165 

stances  made  by  the  bacilli.  It  is  quite  aside  from  the 
present  design  to  discuss  problems  of  immunity,  but  it 
is  perhaps  desirable  to  note  certain  facts  relative  to 
the  protective  action  aroused  by  typhoid  bacilli.  The 
experimental  inoculation  of  human  beings  with  typhoid 
cultures  exposed  to  heat  has  been  shown  by  Wright  to 
result  in  the  following  changes  in  the  blood;  (1)  an  in- 
crease m  the  bactericidal  power  of  the  blood;  (2)  an 
increase  in  bacterioly tic  power  of  the  blood ;  (3)  a  devel- 
opment of  antitoxic  properties  as  indicated  by  the  miti- 
gation of  the  severe  constitutional  signs  of  intoxication 
that  ordinarily  follow  a  first  inoculation  with  typhoid 
vaccine;  (4)  an  increase  in  the  ability  of  the  leucocytes 
to  take  up  and  digest  typhoid  bacilli ;  and  (5)  the  devel- 
opment of  specific  agglutinating  powers  of  the  blood  for 
typhoid  bacilli.  With  the  exception  of  the  agglutinating 
action  of  the  blood,  which  bears  no  definite  relation  to  the 
immunity  of  the  patient,  conditions  similar  to  these 
apparently  constitute  at  least  a  part  of  the  mechanism 
of  defense  hi  the  case  of  typhoid  fever.  How  far  the 
bactericidal  property  of  the  blood  as  measured  in  vitro 
is  an  evidence  of  effective  bactericidal  activity  within 
the  body  is  an  open  question.  Bail  emphasizes  the  fact 
that  an  experimental  immune  serum  which  is  active 
outside  the  body,  does  not  cause  an  effective  solution 
of  typhoid  bacteria  when  injected  with  such  bacteria 
into  the  blood  stream.  The  antitoxic  power  noted  by 
Wright  is  very  likely  dependent  on  "anti-aggressins" 
that  have  arisen  in  response  to  "aggressins."  Effective 
"anti-aggressin"  action  is  probably  extremely  important 


166      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

in  the  struggle  betwee^  the  organism  and  the  bacteria ; 
for  if  the  latter  cannot  restrain  the  natural  protective 
forces  of  the  animal  they  are  attacking,  they  cannot 
efficiently  multiply,  and  they  ultimately  fall  a  victim 
to  the  action  of  the  leucocytes.  During  convalescence, 
after  the  subsidence  of  fever,  the  typhoid  bacilli  found  in 
the  urine  can  hardly  represent  bacteria  that  are  multi- 
plying in  the  blood  and  tissues,  but  rather  are  micro- 
organisms that  have  come  from  the  intestine  from  cer- 
tain foci  in  the  tissues  and  have  escaped  the  action  of  the 
leucocytes  and  bactericidal  serum.  A  state  of  balance 
between  opposing  forces  then  exists,  and  this  may  be 
readily  disturbed  to  the  detriment  of  the  host  by  factors 
favoring  multiplication  of  the  bacilli  in  the  intestine 
(such  as  improper  food)  or  checking  the  formation  of 
"anti-aggressins."  It  is  a  noteworthy  peculiarity  that 
a  patient  may  harbor  the  inciters  of  typhoid  or  cholera 
in  the  intestine  and  still  not  develop  the  specific  disease. 
The  blood  in  these  persons  need  not  contain  an  increase 
in  bactericidal  substances,  and  this  suggests  that  the 
individual  in  question  has  acquired  a  local  immunity 
implicating  the  intestinal  structures,  which  prevents  the 
invasion  of  typhoid  bacilli.  Wassermann  and  Citron 
have  shown  that  immunity  substances  are  made  in 
connective  tissues  as  well  as  in  the  lymphatic  system, 
spleen,  and  bone  marrow,  and  furnish  evidence  pointing 
to  the  possibility  of  inducing  a  local  intestinal  immunity.1 

1  For  a  review  of  the  recent  literature  relating  to  typhoid  fever, 
see  Kolle  and  Wassermann's  "  Handbuch  d.  path.  Mikroorganis- 
men,"  Supplementary  Volume  I,  1906;  Kutscher,  "Abdominal- 
typhus,"  pp.  251,  255,  269,  etc. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT       167 

Paratyphoid  and  Allied  Infections.  —  By  means  of 
careful  biochemical  studies,  including  especially  the  study 
of  the  fermentative  action  on  sugars  (first  systematically 
employed  by  Professor  Theobald  Smith  *)  and  the  agglu- 
tination reactions  and  pathogenic  properties,  it  has  been 
found  that  there  is  an  important  group  of  pathological 
bacteria  which  according  to  their  characters  range  them- 
selves between  the  group  of  colon  bacilli  and  the  typhoid 
bacilli.  The  group  is  large  and  somewhat  heterogeneous 
as  regards  certain  properties,  such-  as  agglutinative  be- 
havior and  pathogenic  qualities.  The  group  includes 
the  inciters  of  hog-cholera,2  of  the  spermophile  disease, 
of  mouse  typhoid,  of  guinea-pig  disease,  of  certain  forms 
of  pseudo-tuberculosis,  of  calves'  diarrhoea,  of  psittacosis 
or  parrot  plague  (which  may  cause  an  atypical  pneu- 
monia in  man),  and  it  includes  the  paracolon  and  para- 
typhoid bacilli,  B.  enteritidis  and  Sanarelli's  bacillus  of 
yellow  fever.3  A  glance  at  this  somewhat  formidable 
list  shows  that  many  of  the  bacteria  in  question  are  the 


Gahrungskolbchen  in  der  Bakteriologie,"  Centralbl. 
f.  Bakt.,  vii,  p.  504,  1890;  "Zur  Unterscheidung  zwischen  Typhus- 
und  Kolonbacillen,"  ibid.,  xi,  p.  367,  1892. 

2  The  agglutinative  characters  of  some  of  the  bacteria  in  this 
group   are   very  similar   though   probably  not   really  identical. 
Thus  Smith  found  the  agglutinative  behavior  of  certain  hog- 
cholera  bacilli  to   be  indistinguishable  from  that  of  Sanarelli's 
bacilli  of  yellow  fever.     It  is  possible  that  common  group  agglu- 
tinins  were  so  abundant  in  the  sera  used  as  to  mask  the  action  of 
very  specific  agglutinins  that  may  have  been  present. 

3  Another  group  of  aberrant  colon-like  bacilli  includes  the  spe- 
cific incitants  of  various  infectious  diseases  of  wild  and  domestic 
birds.     These  organisms  retain  the  ability  to  coagulate  milk  and 
make  indol,  but  differ  from  colon  bacilli  in  showing  weakened 
fermentative  powers. 


168      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

cause  of  animal  diseases.  There  is  little  doubt  that  they 
have  their  normal  habitat  in  the  intestinal  tract  of 
domestic  animals,  and  this  accounts  for  their  very  wide 
distribution  and  for  the  occurrence  of  some  of  them  in 
the  human  intestine.  It  is  especially  those  members  of 
the  group  that  are  pathogenic  for  man  that  interest  us 
here,  and  of  these  we  may  select  for  brief  consideration 
the  bacteria  grouped  under  the  term  "paratyphoid." 

Only  five  years  ago  Schotmiiller  first  maintained  that 
there  are  cases  of  fever  which  run  a  clinical  course 
indistinguishable  from  typhoid  fever  but  differing  from 
it  in  being  incited  by  the  paratyphoid  bacilli.  This 
position  is  now  firmly  established  by  numerous  observa- 
tions ;  for  although  some  of  the  characteristic  lesions  of 
typhoid  fever,  such  as  ulcerated  Peyer's  patches,  are 
relatively  seldom  found  in  paratyphoid  infections,  it 
is  not  clear  that  there  are  any  essential  differences  in 
the  lesions  observed.1  That  the  poisons  made  by  one 
variety  of  paratyphoid  bacilli  are  probably  closely  re- 
lated to  the  poisons  made  by  the  typhoid  bacteria  is 
suggested  by  the  very  close  agglutination  relationships 
that  have  been  discovered  between  these  bacteria. 

It  became  necessary  to  make  a  separation  of  the  para- 
typhoid bacilli  into  two  groups  owing  to  agglutinative 
and  cultural  differences  —  paratyphoid  A  and  B.  The 
bacillus  of  paratyphoid  B  is  probably  widely  distributed. 
It  is  the  cause  of  many  instances  of  disease  running  a 

1  "Weitere  Mittheilungen  iiber  mehrere  das  Bild  des  Typhus 
bietende  Krankheitsfalle,  hervorgerufen  durch  typhusahnliche 
Bacillen  (Paratyphus),"  Zeitschr.  /.  Hyg.,  xxxvi,  p.  368,  1901. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      169 

course  like  that  of  typhoid  fever,  but  as  a  rule  milder  — 
this  milder  course  corresponding  to  the  intermediate 
position  of  the  bacilli  between  colon  bacilli  and  typhoid 
bacilli.  The  justification  for  separating  the  paratyphoid 
bacilli  from  those  of  typhoid  has  been  questioned  by 
some,  but  the  biochemical  distinctions  between  them 
are  definite,  and  as  the  recognition  of  these  distinctions 
is  serviceable  to  man,  it  is  desirable  to  emphasize  them.1 
With  the  recognition  of  these  different  etiological  factors 
the  unity  of  the  condition  we  call  typhoid  fever  is  swept 
away.  This  unity  is  in  fact  still  further  broken  by  the 
fact  that  another  bacillus  of  the  colon  group,  B.  facalis 
alcaligenes,  has  lately  been  shown  to  be  the  inciter  of 
febrile  states  clinically  inseparable  from  mild  forms  of 
the  fever  caused  by  the  typhoid  bacilli. 

It  is  an  inevitable  event  in  the  development  of  bacterio- 
logical science  that  different  investigators  should  some- 
times discover  the  same  microorganism  in  its  relation 
to  different  diseases  and  that  under  these  conditions 
of  discovery  the  organisms  in  question  should  come  to 
bear  different  names.  Thus  it  has  lately  been  insisted 
that  the  bacillus  of  paratyphoid  B  is  identical  with  the 
bacillus  of  mouse  typhoid  and  with  the  well-known 
B.  enteritidis 2  of  Gartner.  In  this  case  the  identity 

1  So  long  as  the  possibility  remains  that  closer  study  may  re- 
veal some  differences  of  a  characteristic  sort  between  the  lesions 
and  pathogenesis  of  the  disease  caused  by  typhoid  bacilli  and  the 
disease  caused  by  paratyphoid  bacilli  it  is  perhaps  permissible  to 
speak  of  the  latter  class  of  cases  as  paratyphoid  fever. 

2  Kutscher  u.  Meinicke,  "  Vergleichende  Untersuchungen  iiber 
Paratyphus-,  Enteritis-,  und  Mausetyphusbakterien  und  ihre  im- 
munisatorischen  Beziehungen,"  Zeitschr.  /.  Hyg.,  Hi,  p.  301,  1906. 


170      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

apparently  does  not  extend  to  completely  reciprocal 
pathogenicity,  for  mouse  typhoid  bacilli  have  never  been 
known  with  certainty  to  cause  the  typhoidal  disease  in 
man,  whereas  the  paratyphoid  bacillus  B  is  pathogenic 
for  mice.1  Of  greater  importance  is  the  fact  that  the 
widely  distributed  bacilli  of  paratyphoid  B  are  cer- 
tainly the  cause  of  many  outbreaks  of  meat  poisoning,2 
and  that  the  bacilli  of  certain  cases  of  meat  poison- 
ing are  identical  with  some  which  cause  typhoid  fever. 
A  highly  instructive  instance  is  one  lately  reported  in 
detail,  in  which  seven  persons  living  hi  one  house  suffered 
from  an  infection  by  paratyphoid  B  bacillus. 

All  the  members  of  a  family  fell  acutely  ill  with  vomit- 
ing, diarrhoea,  and  fever.  At  the  end  of  three  days  the 
temperature  had  returned  to  normal  in  all  the  patients 
except  one,  and  in  this  instance  the  illness  ran  the  course 
of  a  moderately  severe  typhoid,  the  fever  lasting  eighteen 
days.  The  sera  from  all  these  patients  gave  positive 
agglutinations  with  the  bacillus  of  paratyphoid  B. 

Why  it  is  that  some  persons  develop  an  acute  gastro- 
enteritis after  infection  with  this  bacillus  while  others 
have  typhoid  fever,  is  still  somewhat  obscure.  In  cases 
of  meat  poisioning,  the  infected  meat  contains  not  only 
the  bacilli  but  certainly  also  poisons  derived  from  them. 
The  presence  of  these  poisons  accounts  for  the  acute 

1  It  is  also  possible  that  the  use  of  the  absorption  methods  which 
reveal  common  agglutinins  would  show  that  the  agglutinations 
for  these  three  organisms  (now  claimed  to  be  identical)  are  not  in 
reality  absolutely  identical. 

2  Levy  and   Fornet,  "  Nahrungsmittelvergiftung   und  Paraty- 
phus,"  Centralbl.  /.  Bakt.,  Orig.,  xli,  p.  161,  1906. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      171 

onset  of  symptoms.1  The  number  of  bacilli  ingested 
doubtless  exerts  an  important  influence  on  the  character 
of  the  illness.  If  few  bacilli  are  associated  with  the 
poison,  they  usually  do  not  suffice  to  set  up  an  infection, 
and  the  seizure  is  transitory.  If  many  bacilli  are  present, 
they  may  establish  themselves,  freely  multiply,  and  in- 
vade the  organism,  causing  the  phenomena  of  typhoid 
fever.  Hence  in  a  case  where  the  poison  present  in 
the  food  is  associated  with  many  paratyphoid  bacilli, 
the  fever  incidental  to  the  intoxication  may  be  directly 
succeeded  by  a  period  of  fever  due  to  the  bacillary  in- 
fection. Animal  experiment  teaches  that  in  certain 
virulent  bacterial  infections  the  period  of  incubation  is 
in  a  rough  way  inversely  proportional  to  the  number  of 
bacteria  taking  part  in  the  infections.  The  ingestion  of 
very  large  numbers  of  paratyphoid  bacilli  may  thus  be 
followed  by  a  short  period  of  incubation,  whereas  many 
days  may  probably  intervene  before  the  onset  of  fever 
if  the  number  of  bacilli  barely  suffices  for  them  to  gain 
a  foothold  in  the  blood- vascular  and  lymphatic  structures. 
Although  we  have  no  definite  information  on  this  point 
in  the  case  of  paratyphoid  infection,  it  seems  safe  to 
assume  that  the  character  of  the  anti-bacterial  defenses 
of  the  organism  is  a  factor  of  equal  importance  with  the 
number  of  bacilli  in  determining  infection.  These  con- 

1  Dr.  Holt  tells  me  it  is  common  for  typhoid  fever  in  young 
children  to  begin  acutely.  Probably  the  defenses  of  the  digestive 
tract  against  the  bacilli  are  much  feebler  during  infancy  than  in 
later  life,  and  an  insult  from  an  error  in  diet  may  injure  these  local 
defenses  so  as  to  permit  rapid  and  free  multiplication  of  the  typhoid 
bacilli. 


172       INFECTIONS  OF  THE  DIGESTIVE  TRACT 

siderations  regarding  the  influence  of  the  number  of  the 
bacilli  and  the  vigor  of  the  defenses  doubtless  apply  also 
to  the  case  of  infections  with  the  typhoid  bacilli,  but  here 
there  is  probably  never  any  primary  intoxication  from 
the  presence  of  toxins  in  food,  for  the  reason  that  the 
typhoid  bacilli,  requiring  such  special  conditions  for 
multiplication,  do  not  often  find  the  requisite  condi- 
tions for  giving  off  their  poisons  except  within  the  human 
body. 

Dysentery  Bacilli.  —  Very  few  years  have  passed  since 
it  became  apparent  that  certain  microorganisms  which 
had  previously  been  regarded  as  colon  bacilli  are  in 
reality  quite  distinct  from  them  and  stand  in  a  direct 
causative  relation  to  the  widespread  intestinal  disorders 
of  temperate  climates  which  are  grouped  under  the 
term  dysentery.  Takati  Shiga,  a  gifted  young  Japanese 
with  a  German  training,  was  able  to  show  that  the  in- 
testine in  dysentery  contains  large  numbers  of  bacilli 
which,  while  resembling  colon  bacilli  in  some  respects, 
yet  differ  from  them  in  their  fate,  in  their  appearance 
on  agar  plates,  in  their  lack  of  motility,  in  their  failure 
to  make  acid  from  sugar  media,  in  their  failure  to  pro- 
duce indol  or  make  gas,  in  their  power  to  set  up  in  man 
a  disease  clinically  like  dysentery,  and  in  their  ability 
to  confer  on  the  human  blood  serum  the  property  of 
specific  agglutination  in  high  degree.  This  discovery 
was  soon  followed  by  the  researches  of  Flexner  in  Manila, 
which  showed  that  there  is  another  type  of  dysentery 
inciter  allied  to  the  Shiga  bacillus  but  differing  from 
it  in  the  direction  of  retaining  more  fully  some  of  the 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      173 

characters  of  typical  colon  bacilli,  especially  the  capacity 
to  ferment  sugars.  Just  as  in  the  case  of  the  typhoid 
and  paratyphoid  bacilli,  it  is  evident  that  the  bacilli 
farthest  removed  from  colon  bacilli  (the  typhoid  bacilli) 
in  their  characters  incite  the  severest  form  of  the  disease, 
so  in  the  case  of  the  dysentery  bacilli  it  is  true  that  the 
severest  forms  of  disease  are  dependent  on  those  bacteria 
farthest  removed  from  the  colon  bacilli  in  their  biochem- 
ical characteristics;  namely,  the  Shiga  bacilli.  The 
Shiga  bacilli  are  the  cause  of  the  severe  epidemics  of 
Japan  and  of  Germany,  but  in  the  latter  country  bear 
the  name  of  Kruse.  The  Flexner  bacilli  are  apparently 
the  cause  of  dysentery  in  young  children  much  more 
frequently  than  the  Shiga  bacilli.  The  two  types  of 
bacilli  are  further  distinguished  by  their  agglutination 
reactions  and  somewhat  less  sharply  by  their  behavior 
toward  immune  sera.1  The  Shiga  and  Flexner  organisms, 
however,  taken  together  do  not  quite  cover  the  entire 
range  of  bacillary  dysentery ;  for,  as  Park  and  Hiss  have 

1  It  has  been  proposed  to  group  these  types  of  dysentery  bacilli 
under  the  name  paradysentery.  As  it  appears  to  have  been 
conclusively  shown  that  the  lesions  caused  by  these  bacteria  are 
identical  with  those  caused  by  the  Shiga  bacilli,  there  is  no  reason 
why  the  "paradysentery"  bacilli  should  not  be  regarded  as  dysen- 
tery bacilli  equally  with  the  Shiga  organisms.  To  use  the  term 
"paradysentery"  on  the  ground  that  the  bacilli  so  designated  stand 
between  the  Shiga  bacilli  and  the  B.  coli  group  in  cultural,  fermen- 
tative, and  other  characters  does  not  seem  appropriate,  for  there 
are  doubtless  many  bacteria  intermediate  between  the  Shiga  and 
colon  organisms  which  do  not  cause  dysentery.  For  the  present 
it  seems  best  to  employ  the  names  "  Flexner  type  "  and  "  Park-Hiss 
type"  in  referring  to  the  organisms  in  question.  Doubtless 
subdivisions  within  these  types  will  prove  desirable  from  a  bac- 
teriological standpoint. 


174      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

shown,  there  are-  pathogenic  bacteria  intermediate  in 
type  between  the  two.  This  further  distinction  of  a 
third  variety  is  justifiable  on  grounds  of  convenience. 
Indeed,  Shiga1  has  lately  adopted  the  classification  of 
Hiss,  which  recognizes  four  groups  based  on  fermenta- 
tive characters  and  has  added  to  this  a  fifth,  interme- 
diate between  the  acid  bacilli  and  the  non-acid  bacilli. 

Like  the  typhoid  bacilli,  the  bacilli  of  dysentery  are 
hemiparasites ;  that  is,  their  invasive  and  destructive 
properties  are  developed  only  when  the  bacteria  have 
been  introduced  into  the  organism  in  considerable  num- 
bers or  have  had  an  opportunity  to  multiply  owing  to 
feeble  powers  of  resistance  on  the  part  of  the  infected 
individual.  Like  typhoid  bacilli,  the  bacilli  of  dysentery 
form  substances  —  the  so-called  "aggressins"  -which 
are  capable  of  inhibiting  or  even  completely  paralyzing 
the  natural  protective  action  of  the  body  fluids  and  thus 
removing  the  most  important  obstacle  to  the  invasion 
of  the  bacteria  which  up  to  the  moment  of  this  oppor- 
tunity had  led  a  saprophytic  existence.  It  is  not  clear 
whether  these  "aggressins"  are  identical  with  the  soluble 
products  of  the  dysentery  bacilli  which  one  obtains  on 
filtering  an  old  bouillon  culture  or  are  bodies  wholly 
or  in  part  distinct.  It  is  well  established  that  guinea- 
pigs  may  be  actively  immunized  against  the  severest 
intraperitoneal  infection  by  means  of  two  or  more 
injections  of  sterile  guinea-pig  exudate  containing 
"aggressins"  derived  from  the  peritoneal  cavity  of  a  suit- 

1  "Observations  on  the  Epidemiology  of  Dysentery  in  Japan," 
The  Philippine  Journ.  of  Sci.,  i,  p.  485,  1906. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      175 

ably  prepared  animal.  It  has  further  been  found  that 
as  the  result  of  long  preparation  with  such  exudates 
guinea-pigs,  rabbits,  and  sheep  furnish  a  serum  which  in 
amounts  of  one-half  cubic  centimeter  is  able  to  protect 
animals  from  intraperitoneal  infection.  It  is  claimed 
by  Kikuchi l  that  the  immune  serum  obtained  through 
treatment  with  "aggressins"  does  not  show  in  vitro  the 
well-known  characteristics  of  a  bacteriolytic  serum  and  it 
is  maintained  that  this  "  anti-aggressin "  action  is  the 
basis  of  a  new  type  of  immunity.  The  validity  of  the 
latter  claim  cannot  be  successfully  upheld  without  further 
research  in  this  complex  problem.  There  are  now  two 
well-known  antidysenteric  sera  designed  for  human  use : 
one  prepared  by  Shiga  by  immunization  with  the  bacilli 
of  the  originally  discovered  strain  of  dysentery;  the 
other  made  at  the  instigation  of  Dr.  Flexner  by  means  of 
the  variety  of  bacillus  bearing  his  name.  These  sera 
are  regarded  as  being  essentially  bactericidal,  but  there 
is  room  for  doubts  as  to  how  far  the  bactericidal  action 
exhibited  in  vitro  is  operative  after  the  serum  has  been 
put  into  the  dysenteric  patient.  That  these  sera, 
though  not  universally  applicable,  are  quickly  effective 
in  some  instances  of  severe  dysentery  is  certain.  The 
effect  consists  mainly  in  a  diminution  in  the  number  of 
movements,  alleviation  of  tenesmus,  some  lowering  of 
the  temperature,  and  a  calming  of  the  nervous  system 
which  is  sometimes  very  striking.  These  effects  may 

1  "Weitere  Erfahrungen  fiber  Aggressinimmunitat  gegen  den 
Shiga-Kruseschen  Dysenteriebazillen,"  Archiv  f.  Hyg.,  liv,  p.  298, 
1905. 


176      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

depend  in  part  on  an  antitoxic  action,  which  is  perhaps 
mainly  anti-aggressive.  It  seems  clear  that  if  the  solu- 
ble poisons  formed  by  the  dysentery  bacilli  in  the  body 
could  be  promptly  neutralized,  the  bacilli  would  soon 
fall  a  prey  to  the  natural  bactericidal  process  of  the 
serum  and  leucocytes.  It  is  reasonable  to  believe  that 
sera  may  yet  be  obtained  which  will  better  fulfill  this 
need  than  do  those  at  present  in  use.  It  must,  however, 
be  clearly  stated  that  even  a  powerful  antitoxic  or  anti- 
aggressive  serum  could  not  be  counted  upon  to  cure  all 
cases  of  dysentery,  for  in  this  disease  there  is  in  many 
subjects  a  period  when  other  bacteria  than  the  bacilli  of 
dysentery  (especially  streptococci)  enter  the  field  of 
action  in  a  significant  manner.  A  secondary  infection 
of  mixed  character  is  then  set  up,  and  against  this  the 
specific  sera  of  dysentery  must  necessarily  be  ineffective. 
Finally  it  may  be  mentioned  that  there  is  sometimes 
a  therapeutic  difficulty  of  a  wholly  different  character, 
due  to  the  fact  that  a  serum  prepared  with  one  strain 
of  dysentery  bacillus  is  apt  to  be  effective  only  for  this 
strain  and  to  have  little  action  on  other  varieties  of  the 
bacillus.  A  serum  may  thus  be  worthless  in  a  given 
case  because  it  is  not  adapted  to  the  variety  which  is 
acting.  Shiga  has  recently  proposed  the  use  of  a 
universal  or  polyvalent  serum  designed  to  forestall 
embarrassments  of  this  sort.  Shiga's  advice  is  as  fol- 
lows. Two  horses  should  be  simultaneously  immunized, 
one  with  the  bacilli  of  Shiga's  types  I  and  II,  the 
other  with  the  bacilli  of  types  I  and  IV.  As  soon  as 
a  high  grade  of  immunity  is  attained  serum  should  be 


INFECTIONS  OF  THE  DIGESTIVE  TRACT       177 

taken  from  both  horses  and  mixed  in  equal  volumes. 
"By  this  means  the  best  universal  serum  can  be  ob- 
tained" (Shiga). 

I  have  mentioned  that  the  dysentery  bacilli  resemble 
those  of  typhoid  fever  in  being  hemiparasites  capable 
of  infecting  a  susceptible  individual  only  if  present 
in  such  considerable  numbers  that  his  anti-aggressive 
powers  are  neutralized,  thus  clearing  the  way  for  a  free 
multiplication  of  the  bacilli.  There  are,  however,  some 
apparently  fundamental  differences  in  the  biological 
characters  of  these  two  important  pathogenic  forms. 
While  the  typhoid  bacillus,  an  actively  motile  organism, 
is  highly  invasive  and  sets  up  a  bacillsemia  with  con- 
sequences already  noted,  the  dysentery  bacillus,  a  non- 
motile  organism,  is  only  slightly  invasive,  remains  almost 
limited  to  the  intestinal  mucous  membrane,  and  leads 
to  neither  bacillsemia  nor  bacilluria.  The  typhoid  bacilli 
produce  soluble  poisons  with  difficulty,  at  least  in  fluid 
cultures.  Some  dysentery  bacilli,  namely  those  of  the 
original  Shiga  or  promptly  alkali-making  variety,  show 
a  considerable  capacity  to  yield  soluble  poisons  in  fluid 
media.  They  differ  in  this  respect  from  the  acid-making 
varieties,  which  yield  their  active  toxic  product  only 
within  the  animal  organism.1  The  chemical  nature  of 
the  poison  is  at  present  wholly  unknown,  but  significant 
facts  in  respect  to  its  mode  of  action  in  animals,  including 
probably  the  human  species,  have  been  lately  brought 
to  light,  chiefly  through  the  experimental  studies  of 

1  Dr.  Flexner  tells  me  he  has  lately  succeeded  in  obtaining  toxins 
from  his  dysentery  bacilli  by  means  of  a  special  procedure. 


178      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

Dr.  Flexner  1  and  his  associates.  Of  these  facts  the  most 
important  have  to  do  with  the  pathological  alterations 
observed  in  the  intestinal  mucous  membrane  in  the 
course  of  human  dysentery  and  in  the  course  of  experi- 
mental intoxications.  By  intravenously  injecting  into 
rabbits  the  poison  obtained  by  permitting  the  bacilli 
to  undergo  a  process  of  autolysis  or  self-digestion,  Dr. 
Flexner  was  able  to  reproduce  intestinal  lesions  analogous 
to  those  observed  in  human  dysentery ;  namely,  inflam- 
matory, sometimes  diphtheritic  processes,  especially  in 
the  large  intestine  and  often  attended  by  hsemorrhagic 
changes.  It  is  quite  clear  that  these  lesions  are  inciden- 
tal to  an  elimination  of  the  injected  poison  into  the  in- 
testine and  that  the  damage  done  to  the  intestinal 
structures  is  due  primarily  to  the  contact  with  the 
poison  in  the  blood  during  the  act  of  elimination  or 
secretion.  It  seems  probable  that  a  secondary  invasion 
of  the  damaged  structure  by  intestinal  bacteria  forms 
an  essential  part  of  the  dysenteric  process.  These  pri- 
mary eliminative  lesions  are,  as  pointed  out  by  Flexner, 
analogous  to  those  experimentally  called  forth  by 
corrosive  sublimate  and  by  ricin.  I  observed,  many 
years  ago,  hsemorrhagic  and  necrotic  intestinal  lesions  in 
dogs  after  intravenous  infusions  of  urea,  and  these  in- 
juries also  belong  to  the  group  of  eliminative  manifes- 
tations. The  special  value  of  Flexner's  studies  lies,  it 
appears  to  me,  in  the  fact  that  they  show  for  the  first 

1  "The  Pathogenesis  of  Experimental  Colitis,  and  the  Relation 
of  Colitis  in  Animals  and  Man,"  Journ.  of  Exper.  Med.,  viii,  p.  514, 
1906. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT       179 

time  that  the  poison  of  human  pathogenic  bacteria  have 
the  power  of  breaking  down  the  resistance  of  the  intesti- 
nal structures  in  the  eliminative  process.  It  has  always 
been  customary  to  think  of  the  inflammatory,  necrotic, 
intestinal  lesions  of  human  dysentery  as  the  result  of 
strictly  local  conditions,  and  latterly  the  dysentery  bac- 
teria have  fallen  under  suspicion  as  the  inciters  of  the 
lesions,  in  conjunction  with  the  gross  mechanical  insults 
which  might  be  offered  by  the  hard  contents  of  the  lower 
bowel.  Objections  to  this  hypothesis  of  purely  local 
causation  are  the  fairly  even  distribution  of  the  dysentery 
bacilli  through  a  much  larger  extent  of  the  intestine 
than  that  occupied  by  the  severe  lesions,  and,  secondly, 
the  frequent  absence  of  any  ascertainable  local  and  aux- 
iliary factors.  The  newly  acquired  experimental  facts 
force  us  to  look  at  the  local  dysentery  lesions  in  a 
wholly  different  light;  namely,  as  being  perhaps  in 
part  the  result  of  the  action  of  soluble  toxins  which 
have  found  their  way  by  the  blood  to  the  gut  in  a 
changed  (perhaps  autolyzed)  form  and  in  considerable 
concentration.  Although  this  mode  of  origin  cannot 
now  be  positively  affirmed  for  these  local  human 
dysenteric  lesions,  it  must  be  regarded  as  extremely 
probable.  There  is  reason  to  believe  that  the  dysentery 
toxins  are  excreted  in  the  bile  as  well  as  through  the 
intestinal  mucous  membrane.  These  toxins  so  excreted 
may  thus  take  part  in  doing  damage  to  the  intestinal 
structures. 

One  further  phase  of  the  action  of  the  dysentery  poison 
calls  for  mention;  namely,  its  effect  upon  the  nervous 


180      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

system.  Dopter *  has  shown  that  the  toxin  prepared  from 
the  Shiga  bacilli  may  cause  paralysis  in  rabbits  and  that 
this  paralysis  is  usually  referable  to  acute  lesions  in  the 
gray  axis  of  the  spinal  cord  or  ponto-bulbar  region.  As 
the  result  of  the  action  of  a  similar  poison  Flexner  saw 
small  haemorrhages  in  the  brain  and  softening  in  the  gray 
substance  of  the  spinal  cord  with  or  without  haemorrhage. 
Rabbits  are  unequally  susceptible  to  this  nervous  poison 
or  neurotoxin,  and  only  a  small  proportion  of  them  de- 
velop nervous  lesions  after  treatment  with  the  poison, 
whether  this  be  autolyzed  or  not.  The  fact  that  such 
lesions  may  be  sometimes  induced  —  and  perhaps  regu- 
larly under  suitable  experimental  conditions  —  has  a  pos- 
sible bearing  of  great  importance  for  human  pathology. 
It  has  long  been  clear  to  clinicians  that  young  children 
are  susceptible  to  paralyses  referable  generally  to  lesions 
in  the  gray  substance  of  the  spinal  cord  and  that  these 
paralyses  are  apt  to  come  on  at  a  time  of  disordered  intes- 
tinal digestion;  often  indeed  at  the  time  of  teething,  to 
which  process  the  paralysis  has  often  been  somewhat 
vaguely  referred.  As  we  have  only  learned  in  recent 
years  to  see  a  specific  bacillary  dysentery  in  many  cases 
of  slight  intestinal  disorder  in  children,  it  is  likely  that 
many  instances  of  infantile  spinal  paralysis  have  been  as- 
sociated with  a  true  dysenteric  infection.  Of  the  numer- 
ous cases  of  dysentery  that  occur  yearly  in  children,  only 
a  relatively  small  number  are  attended  with  paralyses, 
but  in  view  of  the  experimental  data  now  in  our  posses- 

1  "Effets   exp Sriment aux   de   la   toxine   dysent6rique   sur   le 
systeme  nerveux,"  Ann.  de  I'Inst.  Pasteur,  xix,  p.  353,  1905. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      181 

sion  this  small  number  assumes  a  new  interest.  It  re- 
mains for  the  future  to  definitely  prove  or  disprove  the 
role  of  dysentery  toxin  in  the  causation  of  poliomyelitis. 
I  have  endeavored  to  sketch  with  few  words  some 
of  our  leading  acquisitions  and  problems  in  the  colon- 
typhoid-dysentery  group  of  bacteria  while  touching  only 
lightly  the  realm  of  hypothesis.  It  is  certain  that 
research  will  distinguish  further  varieties  possessing 
interest  for  human  pathology  within  this  large  group. 
Nor  can  we  doubt  that  the  methods  by  which  we  now  seek 
to  combat  the  infections  due  to  members  of  this  group 
will  gain  in  efficiency  and  precision.  Our  attention  has, 
perhaps,  been  too  exclusively  fixed  on  the  specific  excit- 
ants, and  the  role  played  by  associated  bacteria  must  re- 
ceive more  study,  for  it  is  clear  that  they  sometimes  play 
a  significant  part  in  determining  the  outcome  of  an  infec- 
tion. The  difference  that  decides  whether  a  man  will 
live  or  die  must  frequently  be  a  slight  one,  looked  at  from 
the  standpoint  of  the  processes  of  battle  within  the  body. 
To  learn  to  recognize  more  clearly  in  what  this  difference 
consists  and  how  to  use  such  knowledge  to  turn  the  tide 
of  warring  forces  to  the  advantage  of  the  life  that  hovers 
on  the  verge  of  extinction  is  among  the  problems  which 
intelligent,  careful  research  will  help  us  to  solve. 

LIQUEFYING    BACTERIA 

In  the  foregoing  section  has  been  considered  very 
briefly  the  highly  important  group  of  Gram-negative 
microorganisms  which  do  not  liquefy  gelatin  and 
which  are  facultative  anaerobes.  It  is  desired  here 


182      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

to  refer  briefly  to  certain  Gram-negative  facultative 
anaerobes  which  liquefy  gelatin  and  which  are  regarded 
as  having  the  ability  to  induce  putrefaction  in  proteid 
material.  The  most  important  member  of  this  group 
is  the  organism  called  B.  vulgaris,  or  proteus  vulgaris, 
which  is  known  to  make  a  tryptic  ferment  and 
to  peptonize  casein  and  attack  carbohydrates.  It  is 
said  by  A.  E.  Taylor  to  produce  indol,  skatol,  and  diam- 
ino-acids  when  grown  on  casein.  The  organism  is  one 
which  is  sometimes  found  in  moderate  numbers  in  the 
fseces  of  healthy  individuals  where,  as  a  rule,  liquefying 
aerobic  organisms  are  not  numerous.  B.  proteus  vulgaris 
was  formerly  regarded  as  a  very  important  agent  in  the 
production  of  putrefactive  decompositions  outside  the 
body  and  it  has  been  suspected  of  inducing  active  putre- 
faction within  the  human  intestine.  Recent  investiga- 
tions indicate  clearly  that  other  types  of  microorganisms 
belonging  to  the  class  of  strict  anaerobes  are  much  more 
important  factors  in  putrefaction  generally  than  is  the 
B.  proteus  vulgaris,  which  is  sometimes,  however,  asso- 
ciated with  these  anaerobes.  It  appears  that  the  ability 
of  B.  proteus  vulgaris  to  attack  native  proteids  has  been 
overestimated.  I  have  gamed  the  impression  from  the 
study  of  the  action  of  this  organism  on  milk  in  fermenta- 
tion tubes  that  its  peptonizing  action  on  casein  is  ordi- 
narily not  considerable  during  a  period  of  four  to  five 
days'  sojourn  in  the  incubator  at  body  temperature. 
That  B.  proteus  vulgaris  is  capable  of  inducing  acute  dis- 
ease of  the  human  gastro-enteric  tract  appears  to  be  well 
established.  There  are  instances  on  record  of  severe 


INFECTIONS  OF  THE  DIGESTIVE  TRACT       183 

meat  poisoning  apparently  due  to  the  contamination  of 
meat  by  this  organism.  A  number  of  instances  have 
been  recorded  in  which  the  poisoning  following  the  eat- 
ing of  sausages  has  been  attributed  to  the  action  of 
proteus  vulgaris.1  It  has  been  found  in  such  cases  that 
the  nitrate  of  the  bouillon  culture  of  the  proteus  organ- 
ism derived  from  the  contaminated  meat  or  from  the 
intestine  has  been  fatal  to  experimental  animals.  There 
are  also  recorded  some  instances  of  poisoning  through 
cheese  which  had  become  contaminated  by  B.  proteus 
vulgaris.  In  one  instance  a  man  ate  abundantly  of  a 
soft  cheese  containing  this  organism  and  soon  developed 
seizures  of  vomiting  associated  with  great  prostration 
and  cardiac  depression  followed  by  death  after  five 
days.  Other  persons  who  ate  of  the  same  material  more 
moderately  were  similarly  though  less  violently  ill  and 
ultimately  recovered.2 

B.  proteus  vulgaris  is  an  organism  which  in  general 
shows  little  tendency  to  invade  the  circulation  from  the 
digestive  tract  although  it  may  be  the  cause  of  the  sever- 
est gastro-enteric  symptoms. 

Other  Gram-negative  liquefying  facultative  anaerobes 
are  sometimes  found  in  the  human  intestine  in  great 
abundance.  Their  relation  to  the  production  of  disease 
is  not  yet  clearly  established.  Possibly  some  varieties 
of  liquefiers  are  harmless  if  present  in  moderate  numbers. 
In  a  case  of  pernicious  anaemia  from  which  I  was  unable 

1  A  case  of  this  kind  is  that  reported  by  Schumburg,  Zeitschr. 
f.  Hyg.,  xli,  p.  183,  1902. 

2  Berl.  Molkereizeitung,  xiii,  p.  78. 


184      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

to  cultivate  any  colon  bacilli,  the  gelatin  plates  indicated 
the  presence  of  very  large  numbers  of  an  organism  cor- 
responding closely  to  that  described  by  Ford  *  as  B. 
entericus.  This  organism  liquefies  gelatin  with  great 
rapidity. 

Lubenau 2  has  lately  described  a  spore-bearing  Gram- 
positive  aerobic  organism  which  liquefies  gelatin  and 
which  he  looks  upon  as  the  cause  of  an  outbreak  of  severe 
diarrhosa  among  the  inmates  of  an  institution.  This 
outbreak  was  characterized  by  persistent  vomiting,  great 
prostration,  severe  headache,  and  frequently  by  mental 
confusion.  The  diarrhoeal  seizures  were  in  some  in- 
stances as  frequent  as  twenty  or  more  in  twenty-four 
hours  and  were  attended  by  great  abdominal  pain.  The 
general  condition  of  the  patients  improved  rapidly,  but 
the  vomiting  and  diarrhrea  lasted  for  two  or  three  days. 
The  temperature  was  only  slightly  elevated  and  even 
this  slight  rise  was  observed  only  in  a  small  number  of 
the  cases. 

The  organism  described  by  Lubenau  as  the  cause  of 
this  outbreak  resembled  the  common  hay  bacillus  in 
morphology.  It  was  an  actively  motile  aerobe  which 
formed  no  gas  on  sugar-agar  and  attacked  milk  slowly, 
producing  alkali  and  peptone.  It  sporulated  readily 
and  in  its  sporulating  stage  was  non-pathogenic 
for  animals.  When  obtained  hi  large  numbers  in  its 
vegetative  form,  through  growth  upon  milk  to  which 

1  Loc.  tit.,  p.  40. 

2 "  Bacillus  peptonificans  als  Erreger  einer  Gastroenteritis 
Epidemic,"  Centralbl.  f.  Bakt.,  etc.,  I  Abt.,  Orig.,  xl,  p.  433, 
1905-06. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT       185 

Witte's  peptone  had  been  added,  it  induced  pro- 
nounced diarrhoea  in  young  dogs,  sometimes  associated 
with  blood. 


STREPTOCOCCAL   AND   STAPHYLOCOCCAL   INFECTIONS 

The  biological  characters  of  the  streptococcal  and 
staphylococcal  forms  of  bacteria  met  with  in  the  human 
intestine  in  health  and  in  disease  have  not  yet  received 
sufficient  attention.  There  are  indications  that  this  sub- 
ject is  likely  within  a  few  years  to  undergo  a  much- 
needed  development.  In  the  meantime  it  is  impossible 
to  deal  with  the  subject  of  streptococcal  and  staphylo- 
coccal infections  in  a  really  satisfactory  way. 

The  normal  intestine  (both  small  and  large)  usually 
contains  Gram-positive  diplococci  in  moderate  numbers. 
In  culture  media  these  may  grow  freely  in  chains,  the 
individual  organisms  undergoing  division  hi  a  plane 
transverse  to  the  line  of  the  chain  development.  In 
bouillon  cultures  streptococcal  organisms  are  more 
likely  to  maintain  any  virulence  they  may  possess  than 
when  grown  in  sugar  media.  Large  quantities  of  bou- 
illon cultures  of  the  Gram-positive  diplococci  of  the  nor- 
mal intestine  (which  may  have  developed  into  chains 
on  the  bouillon  media)  may  be  injected  into  guinea-pigs 
either  intraperitoneally  or  subcutaneously  without  giving 
rise  to  any  symptoms  or  lesions.  The  human  intestinal 
tract  under  normal  conditions  is  probably  most  of  the 
time  free  from  pathogenic  streptococci  and  in  normal 
adults  such  pathogenic  bacteria  introduced  with  milk  or 


186      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

water  are  ordinarily  quickly  destroyed  in  the  upper  part 
of  the  tract. 

During  infancy  the  digestive  tract  is  much  less  re- 
sistant to  streptococcus  infections,  and  invasion  of  the 
mucous  membrane  by  streptococci  is  a  frequent  occur- 
rence and  may  be  associated  with  disturbances  of  al- 
most any  grade  of  severity.  It  has  been  shown  by 
Booker  in  this  country  and  by  Escherich  in  Germany 
that  some  of  the  severest  forms  of  infantile  ileocolitis 
are  associated  with  streptococcus  infections  and  are 
probably  dependent  upon  them.  As  the  digestive  tract 
of  the  infant  is  readily  damaged  so  as  to  become  per- 
meable by  bacteria,  it  is  not  surprising  that  streptococcus 
septicaemia  is  of  frequent  occurrence.  The  condition  is 
one  which  frequently  but  not  necessarily  ends  fatally. 
A  less  common  result  of  the  penetration  of  the  intestinal 
wall  by  streptococci  is  purulent  peritonitis. 

In  children  there  are  some  instances  of  severe  ileo- 
colitis in  which  streptococci  appear  to  be  the  primary 
inciters  of  disease.  At  least  one  may  say  that  other 
bacteria  which  might  fall  under  suspicion,  such  as  dysen- 
tery bacilli  and  pathological  types  of  colon  bacilli  have 
not  been  found  in  the  cases  in  question.  It  is  doubtful, 
however,  whether  the  biochemical  characters  and  viru- 
lence of  certain  colon-like  forms  have  received  sufficient 
attention  in  those  cases  which  are  regarded  as  instances 
of  pure  streptococcus  infections.  In  many  examples  of 
infantile  diarrhoea  it  appears  clear  that  the  streptococci 
which  are  prominent  in  the  stools  are  really  secondary 
invaders.  Here  the  primary  infection  through  colon 


INFECTIONS  OF  THE  DIGESTIVE  TRACT       187 

bacilli  or  atypical  colon  bacilli  or  dysentery  bacilli 
appears  to  have  prepared  the  way  for  such  a  secondary 
infection.  In  the  case  of  the  dysentery  bacilli  it  is 
probable  that  they  have  the  ability  to  make  "aggres- 
sins"  which  inhibit  the  local  or  even  the  general  defenses 
so  as  to  permit  the  free  multiplication  of  pathogenic 
streptococci.  A  similar  relationship  is  seen  in  some 
instances  of  smallpox,  scarlet  fever,  and  measles.  It 
seems  clear  that  in  many  of  these  cases,  in  which  the  role 
of  the  streptococci  is  that  of  a  secondary  invader,  this 
infection  is  responsible  for  severe  exacerbations  or  death. 
In  adults  the  intestinal  tract  is  not  rarely  the  seat  of 
invasion  by  strep tococcal  microorganisms.  Where  these 
are  virulent,  they  are  apt  to  be  associated  with  diar- 
rhceal  disorders.  There  are,  however,  instances  in  which 
the  streptococci  are  only  slightly  pathogenic  for  animals, 
such  as  guinea-pigs,  but  are  present  throughout  con- 
siderable periods  of  time  in  excessive  numbers  in  the 
stools.  Their  presence  may  be  demonstrated  in  the 
Gram-stained  microscopical  fields,  where  they  are  seen 
as  short  chains  or  as  diplococci.  In  such  cases  these 
organisms  will  be  found  to  be  abundantly  represented 
in  sugar-bouillon  fermentation  tubes  which  have  been  in- 
oculated from  the  mixed  faecal  flora.  We  have  observed 
instances  in  which  these  Gram-positive  streptococcal 
forms  enormously  preponderate  in  the  sedimentary 
fields  from  the  fermentation  tubes.  It  has  some- 
times happened,  also,  that  even  though  the  Gram-posi- 
tive fields  fail  to  show  the  streptococcal  forms  in  such 
abundance  as  to  attract  attention,  they  outgrow  other 


188      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

types  of  bacteria  in  the  fermentation  tubes.  In  one 
instance  in  which  such  an  overgrowth  of  the  fermenta- 
tion tubes  was  regularly  observed  and  in  which  the  move- 
ments regularly  showed  the  presence  of  excessive  num- 
bers of  epithelial  cells,  it  was  found  that  the  patient  had 
for  many  months  been  infecting  himself  daily  from  an  old 
abscess  next  a  carious  tooth.  Although  the  abscess  was 
treated  surgically,  the  improvement  in  the  clinical  con- 
ditions was  very  slow,  and  after  a  period  of  six  months 
under  very  favorable  conditions  of  outdoor  life  evi- 
dences of  streptococcal  infection  still  persisted  to  some 
extent.  In  this  case  loss  of  weight  and  strength,  mental 
depression,  and  moderate  anaemia  were  the  prominent 
clinical  conditions.  The  movements  contained  in  ad- 
dition to  streptococci  somewhat  excessive  numbers  of 
B.  aerogenes  capsulatus. 

The  presence  of  large  numbers  of  intestinal  strep- 
tococci and  diplococci  in  the  faeces  is  a  prominent 
feature  in  some  cases  of  pernicious  anaemia.  The 
significance  of  this  is  not  yet  clear,  partly  because  the 
streptococcal  infection  has  been  associated  in  these 
cases  with  the  presence  of  greatly  excessive  numbers 
of  putrefactive  anaerobes,  especially  B.  aerogenes  cap- 
sulatus. It  seems  probable  that  a  streptococcus  in- 
fection of  the  intestinal  tract  may  greatly  contribute 
to  bring  about  a  deterioration  in  the  physical  condition 
of  a  patient  already  infected  with  the  gas-bacillus.  In 
several  instances  of  severe  anaemia  —  some  of  them 
of  the  pernicious  type  —  a  prolonged  streptococcal 
diarrhoea  has  been  observed  to  precede  the  onset  of 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      189 

more  grave  manifestations  of  alterations  in  the  blood 
and  loss  of  muscular  power. 

It  is  now  well  known  that  there  are  occasional  instances 
of  phlegmonous  gastritis  due  to  streptococcal  infec- 
tions. I  have  observed  instances  of  extreme  hyper- 
chlorhydria  which  showed  in  the  vomited  material  during 
a  seizure  of  protracted  vomiting  large  numbers  of  Gram- 
positive  streptococci  and  many  leucocytes. 

The  relation  of  streptococcus  infections  to  appendicitis 
is  still  unsettled  despite  the  considerable  work  that  has 
been  done  on  the  etiology  of  this  affection.  In  many 
instances  the  dominant  flora  in  the  diseased  appendix 
are  streptococci,  but  the  question  arises  whether  they 
are  primarily  or  secondarily  concerned.  I  have  obser- 
vations on  two  fatal  cases  of  appendicitis  in  which  the 
intestine  between  the  appendix  and  the  anus  contained 
enormous  numbers  of  streptococci  and  diplococci  at  all 
points.  It  appears  to  me  probable  that  the  careful 
microscopical  and  cultural  study  of  the  intestinal  con- 
tents will  prove  an  aid  to  diagnosis  in  some  obscure 
forms  of  local  intestinal  infection  by  streptococci. 

Of  the  position  which  should  be  assigned  to  infections 
of  the  intestinal  tract  by  staphylococci  there  is  little  to 
be  said  at  present.  One  sometimes  observes  in  the  sedi- 
ments of  the  fermentation  tubes  or  bouillon  flasks  which 
have  been  inoculated  from  mixed  faecal  flora  numerous 
clumps  of  Gram-positive  cocci.  The  biochemical  char- 
acters of  these  organisms  have  not  been  studied  and  their 
classification  is  at  present  uncertain.  It  is  noteworthy, 
however,  that  in  two  cases  of  severe  staphylococcus  acne 


190      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

in  which  the  opsonic  index  was  low  for  these  organisms, 
the  mixed  fsecal  flora  regularly  showed  staphylococcal 
forms  in  great  abundance  in  the  sedimentary  fields 
from  the  fermentation  tubes.  Such  organisms,  however, 
have  been  detected  hi  great  abundance  in  the  flora  from 
some  persons  suffering  from  excessive  intestinal  putre- 
faction in  which  acne  was  not  a  feature.  The  very  free 
growth  of  organisms  of  this  type  in  bouillon  inoculated 
with  the  mixed  flora  has  been  observed  especially  in 
the  case  of  material  derived  from  persons  suffering  from 
disorders  of  digestion,  but  it  is  uncertain  what  signifi- 
cance should  be  attached  to  these  observations. 

The  possibility  of  controlling  streptococcal  and  staphy- 
lococcal infections  of  the  digestive  tract  by  means  of  the 
vaccination  methods  employed  by  Wright  is  worthy  of 
serious  consideration.  There  are  cases  of  advanced 
anaemia  in  which  it  appears  likely  that  streptococcus 
infection  is  an  important  etiological  factor,  perhaps 
through  the  agency  of  hsemolytic  poisons  and  certainly 
through  the  causation  of  exhausting  diarrhoea.  If  in 
such  cases  the  streptococcal  element  in  the  infection 
could  be  controlled,  it  seems  clear  that  the  outlook  for 
the  patients  would  be  improved. 

BACILLUS   BIFIDUS 

It  has  already  been  mentioned  that  the  intestinal  tract 
in  childhood  contains  large  numbers  of  the  not  extremely 
anaerobic  microorganism  described  under  the  name  of  B. 
bifidm.  Many  if  not  all  adolescents  and  adults  harbor 
B.  bifidiis,  although  in  smaller  numbers  than  in  early 


INFECTIONS  OF  THE  DIGESTIVE  TRACT       191 

life — a  fact  not  widely  known.  I  have  met  with  excep- 
tionally robust  adults  in  whom  bifidus  was  very  promi- 
nently represented,  if  one  may  trust  the  microscopical 
fields  and  the  primary  *  fermentation-tube  sediments. 
Whether  bifidus  ever  assumes  a  pathological  character  in 
man  is  uncertain.  I  may  refer  here  to  the  observation 
that  a  Gram-positive  bacterium  indistinguishable  from 
typical  bifidus  in  its  microscopical  characters  is  sometimes 
almost  the  exclusive  inhabitant  of  the  lower  digestive 
tract  in  children  with  chronic  intestinal  indigestion  char- 
acterized by  abdominal  distention  and  retarded  growth. 
In  sugar  bouillon  these  fsecal  bacteria  show  the  typical 
varied  morphological  characters  of  B.  bifidus  of  nurslings, 
but  whether  the  organisms  from  these  pathological  cases 
are  really  identical  with  those  obtained  from  the  in- 
testine of  normal  infants  is  uncertain  because  no  ade- 
quate biochemical  observations  have  been  made.  I 
think  the  possibility  should  be  borne  in  mind  that  a  bac- 
terial form  which  is  entirely  physiological  when  dominant 
during  infancy  may  not  be  equally  physiological  when 
it  constitutes  the  dominant  type  in  later  years.  The 
mere  persistence  of  B.  bifidus  as  the  leading  large-intes- 
tinal microorganism  may  carry  with  it  certain  physio- 
logical disadvantages,  such  as  relatively  feeble  powers  of 
defense  against  some  harmful  bacteria. 

INFECTIONS   THROUGH   ANAEROBIC    BACTERIA 

The  anaerobes  of  the  human  intestine  have  received  far 
less  attention  than  the  aerobic  and  optionally  anaerobic 

1  Made  from  direct  inoculation  of  the  faeces. 


192      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

bacteria.  This  neglect  may  be  ascribed  to  the  technical 
difficulties  connected  with  the  study  of  microorganisms 
whose  growth  is  checked  by  minute  traces  of  oxygen, 
and  not  to  any  belief  that  such  microorganisms  are 
unimportant.1  There  is  in  fact  growing  evidence  that 
the  strict  anaerobes  play  an  important  part  in  some 
pathological  processes  which  have  their  seat  in  the  digest- 
ive tract,  and  one  may  hazard  the  prediction  that  careful 
studies  of  them  will  give  us  wholly  new  light  on  some 
obscure  forms  of  disease. 

Bacillus  Putrificus.  —  The  organism  described  by 
Bienstock  as  B.  putrificus  is  a  spore-forming  strict 
anaerobe,  capable  of  actively  attacking  and  hydrolyzing 
native  proteids,  and  like  many  such  anaerobes  able  to 
give  rise  to  characteristic  products  of  putrefaction, 
including  butyric  acid  and  hydrogen.  It  forms  hydro- 
gen sulphide  and  mercaptan  but  not  indol.  Consid- 
erable difference  of  opinion  exists  as  to  whether  B.  putri- 
ficus is  or  is  not  a  regular  inhabitant  of  the  normal 
human  intestine.2  This  question  is  bound  up  with  the 
question  of  the  identity  of  the  bacterium.  Bienstock, 
it  should  be  noted,  has  lately  brought  forward  evidence 

1Tarozzi  ("Ueber  ein  Leicht  in  aerober  Weisse  ausfiihrbares 
Kulturmittel  von  einigen  bis  jetzt  fur  strenge  Anaeroben  gehal- 
tenen  Keimen,"  Centralbl.  f.  Bakt.,  xxxviii,  I  Abt.,  Orig.,  p.  619, 
1905)  has  lately  described  a  method  by  which  it  is  possible  to 
obtain  aerobic  growths  of  organisms  which  have  hitherto  been 
regarded  as  strict  anaerobes,  including  B.  aerogenes  capsulatus, 
B.  botulinus,  etc. 

2  Passini  holds  that  he  can  generally  obtain  it;  Bienstock  states 
that  he  cannot  find  it  in  normal  persons. 

B.  putrificus  is  widespread  and  may  readily  become  a  contami- 
nation as  it  is  common  in  laboratory  dust. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      193 

to  show  that  two  distinct  bacteria  are  included  under 
the  name  of  B.  putrificus.1  One  of  these,  the  true  B. 
putrificus,  attacks  native  proteids  such  as  serum  albumin ; 
the  other,  though  morphologically  indistinguishable  from 
B.  putrificus  fails  to  attack  native  proteids  but  decom- 
poses sugars.  Bienstock  calls  this  organism  B.  para- 
putrificus. He  states  that  he  has  found  it  not  infre- 
quently in  the  normal  human  intestine  and  believes  it  is 
paraputrificus  and  not  putrificus  that  has  been  found  in 
the  contents  of  the  lower  bowel.  As  paraputrificus  makes 
acid  from  sugars  and  does  not  cleave  proteids,  Bienstock 
inclines  to  the  belief  that  the  organism  is  antagonistic 
to  the  true  putrefactive  microorganisms  of  the  intestine 
and  thus  supports  the  colon  bacilli  in  this  function.  But 
it  is  not  clear  that  acid-forming  bacteria  necessarily  act 
as  a  check  to  the  development  of  putrefactive  bacteria 
except  under  special  conditions,  and  it  appears  ques- 
tionable whether  B.  paraputrificus  is  really  a  factor  in 
checking  the  multiplication  of  harmful  anaerobes. 

The  role  of  the  putrefactive  type  of  B.  putrificus  in 
pathological  processes  has  not  yet  been  determined. 
That  it  plays  a  part  in  certain  putrefactive  disorders 
appears  to  me  probable  on  the  following  grounds.  An 
organism  corresponding  to  the  cultural  and  morphological 
characters  of  B.  putrificus  appears  in  great  abundance 
in  week-old  cultures  of  the  mixed  flora  from  some  per- 
sons suffering  from  subacute  or  chronic  intestinal  symp- 
toms at  present  not  satisfactorily  definable.  As  these 
organisms  regularly  appear  after  inoculation  with  the 

1  "Bacillus  Putrificus,"  Ann.  de  VInst,  Pasteur,  xx,  p.  407, 1906. 
o 


194      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

flora  of  these  people,  it  seems  fair  to  assume  that  they 
are  in  these  instances  regular  inhabitants  of  the  digestive 
tract,  although  they  may  not  appear  hi  their  character- 
istic sporulating  form  in  the  microscopical  fields.  The 
flora  of  persons  free  from  symptoms  of  intestinal  derange- 
ment has  not  abundantly  given  us  B.  putrificus  in  our 
bouillon-calcium-carbonate  flasks.  This  is  in  harmony 
with  the  statement  of  Bienstock  that  he  failed  to  find 
B.  putrificus  in  normal  persons.  It  is  true  also  of  the 
intestinal  flora  of  persons  to  whom  the  spores  of  B. 
putrificus  had  been  given  by  the  mouth. 

One  reason  why  it  is  difficult  to  define  with  con- 
fidence the  part  of  B.  putrificus  in  intestinal  processes 
of  putrefaction  is  that  it  is  apt  to  be  associated  with 
other  microorganisms  which  may  be  concerned  with  the 
processes  in  question,  such  as  B.  aerogenes  capsulatus  and 
some  coccal  infections.  The  association  of  excessive 
numbers  of  these  three  organisms  in  the  large  intestine  is 
not  uncommon  in  cases  of  chronic  excessive  intestinal 
putrefaction. 

In  every  instance  in  which  B.  putrificus  is  present  hi 
bouillon  flasks  prepared  by  growing  the  mixed  faecal 
flora  from  cases  of  intestinal  putrefaction,  there  is  found 
also  methyl  mercaptan.  This  observation  corresponds 
to  the  fact  that  B.  putrificus  in  pure  culture  in  peptone 
bouillon  is  capable  of  making  mercaptan.  It  has  not 
always  been  possible  to  grow  B.  putrificus  from  cases 
in  which  a  methyl  mercaptan  reaction  was  obtained, 
and  for  this  reason  and  others  I  believe  that  methyl 
mercaptan  may  be  produced  by  other  intestinal  organ- 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      195 

isms  than  B.  putrificus.  Nevertheless  in  my  experience 
the  strongest  methyl  mercaptan  reactions  have  been 
obtained  from  those  cases  in  which  B.  putrificus  was 
present.  B.  putrificus  grown  in  peptone  bouillon  makes 
more  mercaptan  than  any  other  anaerobe  with  which 
we  have  experimented  in  my  laboratory.  The  mer- 
captan reactions  obtained  from  bouillon  cultures  made 
with  the  mixed  flora  from  some  healthy  young  children 
I  am  disposed  to  attribute  to  B.  putrificus.  This 
organism  is  very  widespread  and  is  present  in  most 
samples  of  dust.  It  is  non-hsemolytic  and  probably 
makes  no  toxins.  Considerable  numbers  of  the  typical 
bacillus  may  be  injected  intraperitoneally  into  guinea- 
pigs  without  causing  noteworthy  damage. 

I  believe  B.  putrificus  to  be  the  most  energetic  an- 
aerobe now  known  in  respect  to  the  ability  to  proteo- 
lyze  native  proteids.  Bienstock's  organism  is  probably 
representative  of  a  group  whose  members  vary  con- 
siderably in  biochemical  properties.  We  have  in  our 
laboratory  a  strain  of  B.  putrificus  of  intestinal  origin 
which  makes  very  large  quantities  of  indol  in  peptone 
bouillon.  It  is  evident  that  the  presence  of  such  an 
organism  in  the  intestine  might  contribute  in  an  impor- 
tant way  to  the  production  of  indol. 

In  a  recent  study  of  the  anaerobic  bacteria  of  the 
mouth,  Dr.  Antonio  Rodella  1  has  ascribed  importance 
to  B.  putrificus  as  a  cause  of  caries  of  the  teeth  and 
inflammation  of  the  pulp.  He  finds  the  substance  of  the 

'"Ueber  anaerobe  Mundbakterien  und  ihre  Bedeutung," 
Archiv  f.  Hyg.,  liii,  p.  329,  1905. 


196      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

teeth  in  caries  to  be  infiltrated  by  this  organism  appar- 
ently in  almost  pure  culture.  Moreover,  he  has  been  able 
to  induce  a  putrefactive  decomposition  in  the  substance 
of  teeth  previously  decalcified  by  the  use  of  acid.  While 
the  evidence  thus  far  brought  forward  in  regard  to  the 
role  of  B.  putrificus  in  causing  disease  of  the  teeth  is  not 
complete  (owing  to  the  difficulty  in  excluding  some 
symbiotic  action  of  other  kinds  of  bacteria),  it  appears 
in  the  highest  degree  probable  that  B.  putrificus  is 
an  important  factor  in  setting  up  caries.  As  this 
organism  is  an  anaerobe,  it  is  easy  to  see  how  scrupulous 
cleanliness  of  the  teeth  and  gums  must  operate  to  pre- 
vent it  from  gaining  a  foothold  in  the  mouth. 

Bacillus  aerogenes  capsulatus.  —  B.  aerogenes  cap- 
sulatus  is  a  strictly  anaerobic,  difficultly  spore-bearing, 
Gram-positive,  gas-making  bacillus.  It  is  found  in 
small  numbers  relatively  to  other  bacteria  in  the  intes- 
tines of  the  majority  of  normal  adults  and  in  still  smaller 
numbers  in  normal  children.  There  are  many  healthy 
breast-fed  and  bottle-fed  children  hi  whom  one  fails 
to  find  evidence  of  the  presence  of  this  microorganism 
in  the  intestinal  tract,  either  through  careful  study  of 
the  Gram-stained  microscopical  faecal  field  or  through 
ordinary  plating  methods.  I  will  not  say  that  the  organ- 
ism is  actually  absent  from  the  intestine  in  these  cases, 
but  it  is  certain  that  if  present  it  is  in  such  small  numbers 
as  to  play  no  appreciable  part  in  the  biochemical  pro- 
cesses that  occur  in  the  digestive  tract.  Our  knowledge 
of  the  part  played  by  this  anaerobe  in  human  pathol- 
ogy has  until  very  recently  been  limited  to  certain 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      197 

surgical  and  obstetrical  diseases.  Some  confusion  has 
arisen  from  the  fact  that  the  organism  is  known  in 
different  countries  under  different  names.  In  Ger- 
many it  is  known  as  the  gas-phlegmon  bacillus  (Fraen- 
kel) ;  in  France,  as  B.  perfringens  (Veillon  and  Zuber) ; 
and  Dr.  Welch  was  able  to  obtain  the  organism 
first  described  by  him  as  B.  aerogenes  capsulatus 
from  a  culture  of  B.  enteritidis  sporogenes  sent  to 
him  by  Dr.  Klein.  The  same  organism  as  B.  aerogenes 
capsulatus  (but  in  a  non-virulent  form)  has  been  de- 
scribed by  Grassberger  and  Schattenf  roh  under  the  name 
of  granulo-bacillus  immobilis  liquefaciens.1  It  occurs 
commonly  in  market  milk. 

Opinions  differ  rather  widely  as  to  the  pathogenic 
properties  of  B.  aerogenes  capsulatus  for  man  and  animals. 
Professor  Welch,2  who  first  discovered  the  organism  in 
connection  with  human  surgical  infections,  was  disposed 
to  regard  it  as  not  being  ordinarily  highly  pathogenic. 
In  reference  to  healthy  rabbits  he  says  we  cannot  regard 
this  bacillus  as  being  pathogenic  under  ordinary  con- 
ditions. Dunham,3  who,  in  the  course  of  his  clever 
investigations  on  B.  aerogenes  capsulatus,  discovered 

1  Professor  Welch  and  some  other  bacteriologists  regard  the 
bacillus  of  Grassberger  and  Schattenf  roh  as  identical  with  B. 
aerogenes  capsulatus  in  everything  except  pathogenicity.  Other 
writers  dissent  from  their  view.  The  two  anaerobes  are  surely 
very  closely  related  if  not  identical. 

'"A  Gas-producing  Bacillus  (Bacillus  Aerogenes  Capsulatus, 
Nov.  Spec.)  capable  of  Rapid  Development  in  the  Blood-vessels 
after  Death,"  by  Wm.  H.  Welch  and  Geo.  A.  F.  Nuttall,  Bull,  of 
the  Johns  Hopkins  Hosp.,  No.  24,  July-August,  1892. 

3  "  Report  of  Five  Cases  of  Infection  by  the  Bacillus  Aerogenes 
Capsulatus  (Welch),"  Bull,  of  the  Johns  Hopkins  Hosp.,  No.  73, 
April,  1897. 


198      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

its  ability  to  make  spores,  ascribes  a  greater  degree  of 
pathogenic  action  to  the  microorganism  with  which 
he  worked  —  these  bacteria  also  having  been  derived 
from  cases  of  surgical  infection.  Grassberger  and 
Schattenfroh,  whose  granulo-bacillus  saccharo-butyricus 
immobilis  liquefaciens  was  derived  from  milk  and  is 
regarded  by  Welch,  Kamen,  and  others  as  identical 
with  B.  aerogenes  capsulatus,  found  it  to  be  non-toxic 
for  guinea-pigs.  Kamen,1  although  unable  to  obtain 
powerful  toxins  on  ordinary  culture  media,  regards 
B.  aerogenes  capsulatus  as  capable,  by  itself,  of  exciting 
inflammatory  purulent  processes.  It  is  certain  that 
there  are  various  strains  of  B.  aerogenes  capsulatus  as 
regards  pathogenicity  and  that  the  different  results 
obtained  by  different  investigators  with  respect  to  that 
feature  are  due  to  this  fact.  Cultures  of  B.  aerogenes 
capsulatus  made  by  Mr.  Ward  from  the  faeces  of  a  young 
man  with  slight  digestive  derangement  and  from  material 
derived  from  a  case  of  pernicious  ansemia  were  injected 
into  the  breast  muscles  of  pigeons  (according  to  a  sug- 
gestion from  Dr.  Flexner,  who  had  found  these  animals 
to  be  especially  susceptible).  The  cultures  set  up  a 
localized  necrotic  inflammation  with  gas  production  in 
the  connective  tissues.  Death  occurred,  apparently 
from  toxaemia,  within  twenty-four  hours.  The  applica- 
tion of  these  facts  to  capsulatus  infection  of  the  intestine 
is  not  now  clear.  It  is  certain  that  the  pathogenicity 
of  B.  aerogenes  capsulatus  is  different  for  different 
strains  isolated  from  the  human  digestive  tract.  Thus 

1  "Zur  Aetiologie  der  Gasphlegmone,"  Centralbl.  /.   Bakt.,  I 
Abt.,  Orig.,  xxxv,  pp.  554,  686,  1904. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      199 

Professor  Theobald  Smith  sent  us  an  organism  (anaerobe 
xxxi)  which  he  isolated  from  the  stool  of  a  patient  with 
pernicious  ansemia  and  which  proved  to  be  much  less 
pathogenic  for  guinea-pigs  than  the  typical  form  of  B. 
aerogenes  capsulatus.  This  organism  differed  but  slightly 
from  the  typical  bacillus  in  its  morphology,  but  showed 
the  important  peculiarity  of  being  non-haemolytic.  It 
fermented  the  various  sugars,  but  the  gas  production 
was  less  abundant  than  in  the  case  of  the  typical  gas- 
bacillus.  The  gas  production  and  decomposition  in- 
duced in  an  incubated  rabbit  were  also  less  pronounced 
than  in  the  case  of  the  typical  B.  aerogenes  capsulatus. 

A  single  observation  was  made  by  Mr.  Ward  on  the 
blood  serum  from  a  patient  with  pernicious  anemia 
(and  capsulatus  infection  of  the  intestine)  with  respect 
to  a  possible  agglutinative  action.  The  results  were 
entirely  negative.1  It  is  interesting  to  note  in  this  con- 
nection that  Kamen  2  obtained  no  agglutinative  action 
from  the  serum  of  rabbits  which  had  been  immunized 
with  the  gas-bacillus.  Positive  results  have,  however, 
been  recently  obtained  by  Werner,3  who  employed  a 
special  technical  procedure  in  the  immunization  of  the 
rabbits  which  served  as  experimental  animals.  The 
immune  serum  caused  agglutination  of  the  homolo- 
gous gas-phlegmon  bacilli  (derived  from  a  gas  liver  found 
in  a  fatal  case  of  wound  infection)  in  a  dilution  of  1 : 1000. 

1  Professor  Theobald  Smith  tells  me  that  he  obtained  negative 
results  in  agglutinative  tests  made  with  the  blood  of  a  patient 
with  pernicious  anaemia  who -showed  large  numbers  of  B.  aerogenes 
capsulatus  in  the  faeces.  2  Loc.  tit. 

3  "  Die  Agglutination  bei  Gasphlegmonbacillen,"  Archiv  f.  Hyg., 
liii,  p.  128,  1905. 


200      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

Passini 1  obtained  positive  results  in  some  of  his  cases 
not  only  with  homologous  strains  but  also  with  unre- 
lated ones.  In  this  case,  however,  the  agglutinative 
action  of  the  immune  serum  was  less  marked  than  in  the 
case  of  the  sera  obtained  by  Werner.  It  is  evident  that 
there  is  still  much  to  be  learned  in  relation  to  the  im- 
munizing action  of  B.  aerogenes  capsulatus  and  that  such 
an  action  hi  man  may  yet  be  discovered. 

The  organisms  we  have  classed  as  belonging  to  the 
B.  aerogenes  capsulatus  type  are  large,  plump,  usually 
straight  bacilli,  which  as  they  occur  in  the  faeces,  can 
usually  be  shown  to  be  provided  with  a  capsule.  Organ- 
isms which  have  developed  in  a  living  or  dead  rabbit 
always  acquire  capsules.  The  organisms  occur  very 
often  in  pairs,  end  to  end,  sometimes  singly ;  sometimes 
in  chains;  sometimes  as  threads,  which  may  be  nearly 
straight  or  sharply  bent  on  themselves.  The  ends  of 
adjacent  bacilli  are  slightly  rounded  or  squared,  though 
not  so  sharply  squared  as  in  the  case  of  anthrax  bacilli. 
They  are  immobile  when  viewed  in  hanging  drops. 
Spore  formation  occurs  with  difficulty ;  i.e.  chiefly  under 
very  special  conditions,  such  as  on  a  medium  containing 
blood  serum  or  within  the  body  of  an  animal.  Occa- 
sionally spore  formation  is  seen  in  blood-agar  colonies, 
the  bacilli  from  which  in  other  respects  conform  to  the 
characters  of  B.  aerogenes  capsulatus.  On  sugar  bouillon 
gas  formation  is  abundant  and  rapid,  twice  as  much  gas 
(or  more)  being  formed  in  twenty-four  hours  as  is  usually 

1  "Variabilitat  der  Bakterien  und  Agglutinatinosphanomen," 
Munch,  med.  Wochenschr.,  li,  p.  1283,  1904. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      201 


formed  by  organisms  of  the  B.  coli  group.  The  gas 
consists  of  from  one-third  to  one-half  carbon  dioxide, 
the  remaining  gas  consisting  mainly  of  hydrogen.1  The 

1  Professor  Theobald  Smith  gives  the  following  gas  formula  for 
B.  aerogenes  capsulatus :  — 

H         2  =3 
CO2      1       2 

The  following  table  illustrates  the  approximate  ratio  of  hydro- 
gen and  carbon  dioxide :  — 


Source  of  Microorganism 

Medium 

Height  of  Gas 
Column  in  Milli- 
meters (in  24 
hours) 
Height  of  anaero- 
bic limb  95  mm. 

H 
C02 

1  .   Young  man  with  slight  di- 
gestive derangement 

Milk 

87 

I 

- 

Dextrose- 
bouillon- 
blood 

7 

f 

2.  Same  case  as  No.  1 

Milk 

75 

f 

«          „ 

Dextrose- 
bouillon- 
blood 

80 

f 

3.  Pernicious  ansemia 

Milk 

60 

f 

« 

Dextrose- 
bouillon- 
blood 

75 

f 

4.  Pernicious  ansemia 

Milk 

70 

1 

5.  Pernicious  ansemia 

Milk 

100 

f 

« 

M 

85 

f 

6.  Pernicious  ansemia 

Milk 

90 

f 

7.   Same  case 

Milk 

84 

I 

8.  Aerobic  capsulate  bacillus 

Milk 

87 

f 

9.  Milk 

Milk 

90 

\ 

10.  Milk 

Milk 

85 

| 

202      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

gas  production  in  incubated  rabbits  is  very  rapid  and  is 
associated  with  a  characteristic  sweetish,  sickening  odor  of 
butyric  acid  mixed  with  some  unknown  constituent  or 
constituents.  The  gas  obtained  from  the  peritoneal  cav- 
ity and  connective  tissues  gives  the  hydrogen  "  bark"  and 
burns  with  a  blue  flame.  The  liquefaction  of  muscles, 
liver,  etc.,  is  remarkably  rapid  in  such  incubated  rabbits. 
Grown  on  pasteurized  milk,  the  bacteria  in  question  induce 
rapid  gas  formation  ("stormy  fermentation")  with 
disruption  of  curds  into  small  masses  and  peptonization 
of  casein.  They  do  not  quickly  produce  hydrogen 
sulphide  or  methyl  mercaptan  on  ordinary  sugar-free 
media,  but  may  perhaps  make  these  sulphur  compounds 
more  readily  on  milk.  Grown  in  fermentation  tubes 
containing  blood  bouillon,  they  rapidly  liberate  haemo- 
globin. The  organisms  are  strictly  anaerobic  and  many 
of  their  colonies  on  blood  agar  appear  after  two  or  three 
days  as  minute  points  which  lie  beneath  the  surface  and 
develop  into  fuzzy  spheres.  These  spherical  colonies 
often  have  dark  centers.  The  microorganisms  induce 
inflammatory  necrotic  changes  with  gas  formation  when 
injected  into  susceptible  animals,  such  as  pigeons. 

As  first  shown  by  Professor  Theobald  Smith,  B.  aero- 
genes  capsulatus  usually  grows  readily  on  bouillon  in  the 
closed  arm  of  the  fermentation  tube  provided  small 
bits  of  sterile,  fresh  tissue  are  introduced  into  it.  The 
liver  of  the  guinea-pig  may  advantageously  be  used. 
The  presence  of  the  tissue  probably  favors  the  growth 
in  two  ways :  by  furnishing  a  constituent  of  the  medium 
necessary  for  the  growth  of  the  organism,  and  by  in- 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      203 

ducing  a  more  strict  condition  of  anaerobiosis  by  the 
reducing  activity  of  the  cells. 

If  we  cultivate  B.  aerogenes  capsulatus  on  sugar 
bouillon  we  find  that  it  is  a  large  producer  of  gas  (mainly 
hydrogen  and  carbon  dioxide)  and  that  it  makes  butyric 
and  closely  related  acids  in  abundance,  while  the  forma- 
tion of  lactic  acid  is  small.  On  media  which  contain 
very  little  sugar  but  much  proteid,  the  organism  is 
still  able  to  make  gas  in  considerable  amounts,  though 
less  freely  than  on  a  sugar  medium,  in  which  the  libera- 
tion of  gas  is  remarkably  rapid.  In  nearly  sugar-free 
media  the  gas  bacillus  produces  butyric  acid,  and  the 
quantity  of  this  hi  old  cultures  may  be  surprisingly 
great.  Ammonia  is  formed  at  the  same  time  and  serves 
to  neutralize  at  least  in  part  the  acid  which  is  simul- 
taneously made.  Most  varieties  of  the  organism  are  not 
indol  producers  when  grown  alone  in  blood  bouillon. 
There  are  strains  which  make  indol. 

More  important  for  the  pathologist  than  any  of  these 
substances  is  the  formation  of  a  moderately  hsemolytic 
substance  (or  substances)  by  the  gas-bacillus.  Evidence 
of  such  substances  was  obtained  in  a  five-day  culture 
of  capsulatus  in  blood  bouillon.  One-half  of  one  cubic 
centimeter  of  the  filtrate  from  this  culture  induced 
haemolysis  in  a  suspension  of  rabbit's  red  cells  prepared 
by  Ehrlich's  method,  the  filtrate  having  been  carefully 
neutralized  to  the  litmus  point.  The  same  result  was 
obtained  in  the  case  of  red  cells  from  a  large  Rhesus 
monkey.  Treatment  of  this  filtrate  in  an  exhaustion 
apparatus  very  slightly  reduced  the  hsemolytic  action; 


204      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

heating  to  70°  C.  for  one  hour  reduced  it  still  further; 
but  even  boiling  did  not  wholly  destroy  it. 

In  order  to  determine  whether  this  hsemolytic  action 
was  dependent  in  part  on  volatile  ammonium  com- 
pounds, the  capsulatus  filtrate  was  rendered  distinctly 
alkaline  with  sodium  carbonate  and  concentrated  under 
reduced  pressure  at  a  low  temperature  for  the  removal 
of  ammonia.  The  filtrate  was  then  restored  to  its 
original  volume.  It  was  found  that  the  hsemolytic 
action  of  the  fluid  was  somewhat  diminished  but  not 
lost. 

The  hsemolyzing  action  of  B.  aerogenes  capsulatus  is 
very  clearly  shown  in  fermentation  tubes  containing 
sugar-blood  bouillon  which  have  been  inoculated  with 
pure  cultures.  A  free  liberation  of  haemoglobin  occurs  in 
twenty-four  hours  or  less.  A  similar  result  is  seen  in  the 
case  of  an  aerobic  organism  closely  resembling  B.  aero- 
genes  capsulatus  in  morphology.  The  bacillus  of  malig- 
nant oedema  does  not  exert  a  hsemolyzing  action  under 
similar  conditions.  B.  putrificus  was  found  to  reduce 
hemoglobin,  but  this  change  is  much  less  marked  in  the 
case  of  B.  aerogenes  capsulatus. 

There  are  other  indications  that  B.  aerogenes  capsulatus 
makes  a  hsemolytic  substance  or  ha3molytic  substances. 
Rabbits  injected  with  pure  cultures  of  B.  aerogenes  capsu- 
latus and  then  incubated  at  37°  C.  soon  show  indications 
of  haemolysis,  whereas  control  animals  subjected  to  the 
same  procedure  do  not  exhibit  an  equal  degree  of  hee- 
molytic  change  in  the  same  period  of  time.  This  corre- 
sponds with  the  observation  that  advanced  haemolysis 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      205 

is  usually  noted  in  persons  who  at  autopsy  show  signs  of 
general  invasion  of  the  gas-bacillus. 

The  capacity  of  B.  aerogenes  capsulatus  to  form  poisons 
is  apparently  not  limited  to  haemolytic  and  proteo- 
clastic  substances.  Kamen  *  states  that  when  the  sporo- 
genic  form2  of  the  organism  is  grown  on  a  suitable 
medium  it  forms  soluble  poisons  (obtainable  in  the 
filtrate)  which  are  capable  of  inducing  in  rabbits  a  state 
of  nervous  excitation  followed  by  general  convulsions 
and  paralysis  of  respiration.  He  found  that  one-half  to 
one  and  one-half  cubic  centimeters  is  fatal  for  one  kilo- 
gram rabbit  in  one-half  to  one  minute.  Kamen  likens 
the  material  studied  by  him  to  Faust's  "sepsin,"  hi  that 
it  acts  as  a  respiratory  poison  and  induces  vomiting, 
bloody  diarrhoea,  tenesmus,  and  death.  These  gastro- 
enteric  symptoms  are  associated  with  oedema  and  hy- 
persemia  of  the  gastro-enteric  tract.  The  poisonous 
substances  in  question  are  said  to  be  dialyzable  and 
not  destroyed  by  heating  for  fifteen  minutes  at  60°  C.  I 
have  been  unable  to  confirm  these  observations  by  means 
of  filtrates  prepared  from  cultures  of  the  vegetative  form 
of  B.  aerogenes  capsulatus,  but  it  is  distinctly  stated  by 
Passini  that  the  products  of  the  sporogenic  and  asporo- 
genic  forms  of  the  organism  are  different. 

I  think  it  important  to  determine  whether  B.  aerogenes 
capsulatus  is  able  to  produce  substances  injurious  to  the 

1  "Zur  Etiologie  der  Gasphlegmone,"  Centralbl.  f.  Bakt.,  Orig., 
xxxv,  pp.  554,  686,  1904. 

2  This  form  of  the  organism  was  obtained  by  growing  the  com- 
mon vegetative  form  on  an  egg-and-bouillon  medium. 


206       INFECTIONS  OF  THE  DIGESTIVE  TRACT 

nervous  system.  Persons  suffering  from  severe  forms  of 
chronic  infection  by  this  organism  almost  always  show 
signs  of  intoxication  of  the  nervous  system,  but  such 
manifestations  are  very  different  in  different  individuals. 
It  is  not  yet  clear  whether  the  gas-bacillus  makes 
a  substance  capable  of  exciting  an  acute  inflamma- 
tion of  the  ileum  or  colon  or  whether  preceding 
mechanical  or  chemical  irritation  is  necessary  to  enable 
the  organism  to  multiply  rapidly  and  excite  further 
inflammation.  Healthy  monkeys  may  be  fed  consider- 
able numbers  of  capsulati  without  developing  signs  of 
inflammation  in  the  intestine,  although  such  feeding  is 
followed  by  an  increase  in  these  organisms  in  the  faeces. 
Two  monkeys  fed  on  gas  livers  from  incubated  rabbits 
infused  with  pure  cultures  of  B.  aerogenes  capsulatus 
developed  soft  stools  temporarily.  Such  experiments 
are,  however,  quite  different  from  the  experiment  of 
introducing  capsulati  into  a  digestive  tract  already 
somewhat  inflamed  and  irritable  in  consequence  of  pre- 
ceding infections.  The  ability  of  B.  aerogenes  cap- 
sulatus  to  cause  an  inflammatory  necrotic  process  in  the 
muscles  of  guinea-pigs  and  pigeons,  which  was  noted 
by  Dr.  Flexner  many  years  ago,  is  of  interest  in  this 
relation.  It  appears  probable  that  B.  aerogenes  cap- 
sulatus is  often  the  cause  of  slight  inflammatory  or  per- 
haps even  necrotic  changes  in  the  mucous  membrane 
of  the  intestine.  Howard  *  has  described  instances  of 

1  "Contributions  to  the  Science  of  Medicine,  Dedicated  by  his 
Pupils  to  William  Henry  Welch  on  the  25th  Anniversary  of  his 
Doctorate,"  Baltimore,  p.  461,  1900. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      207 

superficial  necrosis  of  the  mucous  membrane  of  the 
stomach  and  intestine,  associated  with  the  presence  of 
capsulatus  in  abundance.  These  necrotic  areas  most 
often  lie  beneath  the  folds  of  the  valvulse  conniventes  and 
may  occur  with  gas  cysts.  It  does  not  seem  likely  that 
B.  aerogenes  capsulatus  is  responsible  for  severe  acute 
inflammatory  lesions  of  the  intestine,  but  it  is  probable 
that  its  activities  will  account  for  the  subacute  enteritis 
that  is  so  often  present  in  cases  that  show  large  numbers 
of  the  bacilli  in  the  stools.  It  is  certain  that  there  are 
instances  of  acute  diarrhoea  associated  with  very  free 
capsulatus  multiplication  and  such  diarrhoeas  are  com- 
mon in  persons  with  severe  primary  anaemia.1 

In  1905  Tissier 2  described  an  acute  intestinal  affection, 
especially  frequent  in  nursling  children,  which  he  ascribed 
to  the  presence  of  almost  pure  cultures  of  B.  perfringens. 
He  claimed  that  in  the  treatment  of  these  perfringens  diar- 
rhoeas which  ordinarily  ran  a  mild  course  the  most  effica- 
cious therapeutic  agency  was  the  employment  of  cultures 
of  a  lactic  acid  bacillus  (B.  paralacticus) .  I  have  in  a  few 
instances  met  with  acute  and  subacute  diarrhceal  affec- 
tions of  children  in  which  B.  aerogenes  capsulatus  may  per- 
haps have  been  the  cause  of  the  intestinal  derangement, 
although  in  these  cases  pathogenic  varieties  of  colon 
bacilli  have  not  been  absolutely  excluded  as  causal  agents. 

1 1  am  disposed  to  attribute  this  diarrhrea  to  an  associated 
streptococcus  infection  in  these  cases.  One  may  observe  cases 
of  advanced  infection  with  the  gas-bacillus  without  any  diarrhoea; 
indeed  obstinate  constipation  is  found  in  some  of  them. 

2  "Etude  d'une  varie"te"  d'infection  sur  le  nourrisson,"  Ann. 
de  I'lnst.  Pasteur,  xix,  p.  273,  1905. 


208      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

In  this  connection  it  should  not  be  forgotten  that  Klein 
isolated  from  the  fseces  in  an  outbreak  of  diarrhoea  an 
organism  which  very  probably  is  identical  with  B. 
aerogenes  capsulatus.  This  organism  was  given  the  name 
B.  enteritidis  sporogenes.  The  position  of  the  organism 
described  by  Klein  is  open  to  some  suspicion  because 
while  it  is  stated  by  him  to  produce  gas  and  butyric  acid 
in  the  very  characteristic  manner  observed  by  Welch 
and  Nuttall  for  B.  aerogenes  capsulatus,  it  differs  from 
the  latter  in  having  motility  and  apparently  in  sporulat- 
ing  much  more  readily.  Cultures  sent  by  Dr.  Klein  to 
Professor  Welch  contained  bacilli  which  agreed  in  every 
detail  with  pure  cultures  of  B.  aerogenes  capsulatus.1 
As,  however,  the  faeces  sometimes  contain  bacteria 
having  the  morphology  of  B.  aerogenes  capsulatus  but 
differing  from  this  organism  in  forming  spores  much 
more  readily,  it  is  possible  that  Klein  was  in  reality 
dealing  with  impure  cultures  of  B.  aerogenes  capsulatus. 
I  am  disposed  to  believe,  after  a  careful  review  of  the 
available  evidence  on  the  subject,  that  Klein  had  an 
organism  distinct  from  B.  aerogenes  capsulatus,  though 
he  may  have  had  this  also. 

B.  aerogenes  capsulatus  belongs  in  the  group  of  anaerobic 
putrefactive  microorganisms  capable  of  making  butyric 
acid  and  hydrogen.  If  careful  biochemical  tests  be  made, 
there  is  no  difficulty  about  distinguishing  the  gas-bacillus 
from  other  anaerobes  that  occur  in  the  human  diges- 
tive tract.  The  bacillus  of  malignant  oedema  is  some- 

1  See  "Manual  of  Bacteriology  by  Muir  and  Ritchie,"  American 
Edition,  p.  354,  1904. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      209 

times  found  in  the  human  intestine.  Whether  it  is 
ever  found  in  large  numbers  or  ever  possesses  patho- 
logical significance  is  at  present  unknown.  The  bacil- 
lus of  malignant  oedema  resembles  the  gas-bacillus  in 
morphology,  but  sporulates  more  readily,  is  motile,  and 
forms  less  gas  on  sugar  media.  Its  behavior  on  milk  is 
wholly  different  from  that  of  the  gas-bacillus.  When 
injected  into  a  living  rabbit  which  is  subsequently  killed 
and  incubated  it  is  found  that  there  has  been  little  or 
no  liberation  of  gas  in  the  liver  and  elsewhere  —  a 
feature  which  easily  distinguishes  it  from  B.  aerogenes 
capsulatus.1  An  organism  which  closely  resembles  B. 
aerogenes  capsulatus  in  many  respects  is  the  bacillus  of 
rauschbrand  or  symptomatic  anthrax  (the  cause  of  the 
quarter-evil  or  black-leg).  This  organism  is,  however, 
frequently  Gram-negative  under  conditions  of  staining 
in  which  the  gas-bacillus  is  Gram-positive;  it  is  also 
motile.  It  resembles  B.  aerogenes  capsulatus  in  being 
an  abundant  gas  producer,  the  gas  formed  showing  a 
relation  between  hydrogen  and  carbon  dioxide  closely 
resembling  that  obtained  from  the  gas-bacillus.  This 
organism  is  the  only  one  of  the  anaerobes  which  I  have 
found  to  be  able  to  give  rise  to  a  large  production  of  gas 
in  an  incubated  rabbit.  It  might  be  supposed  that  this 
organism  could  be  mistaken  for  the  gas-bacillus,  but  I 
think  the  difference  in  the  conditions  of  sporulation  would 

1  Ghon  and  Mucha  gave  a  comparison  of  the  gas-bacillus  with 
the  bacillus  of  malignant  redema  and  a  third  organism  (derived 
from  a  case  of  peritonitis)  closely  related  to  these  ("Beitrage 
zur  Kentniss  der  anaeroben  Bakterien  des  Menschen,"  Cen- 
tralbl.  f.  Bakt.,  Orig.,  xl,  p.  37,  1905-06). 


210       INFECTIONS  OF  THE  DIGESTIVE  TRACT 

suffice  to  make  the  distinction.  It  was  found  that  in  the 
rabbit  test  the  rauschbrand  bacillus  sent  me  by  Dr. 
Theobald  Smith  sporulated  very  freely  and  characteris- 
tically in  the  blood  and  spleen  and  liver.  We  have 
never  observed  sporulation  on  the  part  of  B.  aerogenes 
capsulatus  within  the  body  of  a  rabbit  incubated  accord- 
ing to  the  Welch-Nut  tall  method.  Whether  the  bacillus 
of  rauschbrand  ordinarily  occurs  in  the  human  intestine 
is  questionable.  It  seems  unlikely  that  it  should  be 
found  there  except  in  the  case  of  persons  living  in  asso- 
ciation with  infected  cattle. 

Bacillus  botulinus.  —  Botulism  is  a  variety  of  meat 
poisoning  in  which  the  pathological  effects  are  due  to  a 
powerful  soluble  poison  made  by  a  strict  anaerobe,  these 
effects  being  exerted  mainly  on  the  central  nervous 
system.  The  organism  in  question  resembles  in  some 
respects  B.  aerogenes  capsulatus}  and  in  others  the  bacillus 
of  tetanus.1  It  was  isolated  in  1896  by  Van  Ermengen 
from  a  sample  of  ham,  the  eating  of  which  in  a  raw  state 
had  caused  many  instances  of  poisoning  and  some  with 

1  B.  botulinus  possesses  a  varied  morphology,  sporulates  ter- 
minally, makes  little  gas  on  sugar-blood  bouillon,  and  is  motile. 
The  specimen  sent  to  me  by  Krai  as  Van  Ermengen 's  B.  botulinus 
was  introduced  into  a  rabbit  and  subjected  to  the  incubation  test. 
It  was  found  that  the  liver  was  in  an  advanced  state  of  putrefac- 
tion, but  neither  this  organ  nor  any  other  part  of  the  body  showed 
even  the  slightest  indications  of  gas  formation.  It  is  noteworthy 
that  the  vegetative  form  of  the  organism  (which  is  the  form  in 
which  the  botulinus  bacillus  was  introduced)  showed  evidence  of 
sporulation  in  the  spleen  but  not  in  the  blood  or  the  liver.  An 
absorption  test  made  by  Mr.  Ward  showed  that  the  gas  formed  by 
this  bacillus  on  dextrose-blood  bouillon  consisted  of  four  parts 
carbon  dioxide  to  one  part  of  hydrogen. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      211 

fatal  ending.  The  symptoms  closely  resembled  those  of 
the  so-called  cases  of  sausage  poisoning  which  had  been 
reported  from  time  to  time.  Very  recently  the  interest- 
ing fact  has  developed  in  a  Darmstadt  outbreak  that 
the  same  type  of  poisoning  may  occur  from  eating  vege- 
table food ;  namely,  in  this  instance,  beans  which  were 
imperfectly  canned.1  It  appears  probable  that  the  beans 
were  infected  through  the  use  of.  manure  obtained  from 
pigs. 

The  following  are  the  leading  symptoms  of  classical 
botulism:  first,  disturbances  of  the  external  muscles 
of  the  eyeball,  especially  ptosis,  abducens  paralysis,  and 
disturbances  of  associated  movement  with  nystag- 
mic  contractions;  second,  disturbances  of  the  internal 
muscles  of  the  eye.  In  the  majority  of  instances  there 
have  been  paralyses  of  accommodation.  In  the  Darm- 
stadt outbreak  from  infected  beans  an  enlargement  and 
rigidity  of  the  pupils  was  never  observed,  but  in  the  out- 
breaks from  meat  poisoning  these  pupillary  conditions 
have  been  usually  noted.  Third,  there  are  usually 
derangements  referable  to  the  region  of  the  pons  and 
medulla  oblongata,  including  disorders  of  the  tongue, 
such  as  swelling  and  paralysis,  pharyngeal  and  laryn- 
geal  paralyses  and  disturbances  of  the  heart  and  respira- 
tion. Fourth,  weakness  and  even  paralysis  of  motion 
may  appear.  These  disturbances  have  almost  always 
been  unaccompanied  by  changes  in  sensibility  and 

1  Fischer,  "  Ueber  eine  Massenerkrankung  an  Botulismus  in- 
folge  Genusses  verdorbener  Bohnenkonserven,"  Zeitschr.  f.  klin. 
Med.,  lix,  p.  58,  1906. 


212      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

consciousness ;  fever  has  been  absent  and  there  has  been 
an  absence  of  disturbances  of  the  stomach  and  intestine. 
The  symptoms  seldom  come  on  before  twelve  to  twenty- 
four  hours  after  the  ingestion  of  the  poison.  Very 
similar  symptoms  were  produced  by  Van  Ermengen  in 
certain  animals  by  giving  them  watery  extracts  of  the 
infected  ham  or  cultures  either  by  the  stomach  or  by 
subcutaneous  injections.  It  is  noteworthy  that  in  these 
animal  experiments  there  was  observed  a  period  of  in- 
cubation of  not  less  than  six  to  twelve  hours  before  the 
onset  of  symptoms.  The  characteristic  paralytic  effects 
can  be  induced  by  means  of  the  filtered  toxin,  and  it  is 
therefore  clear  that  the  phenomena  of  botulism  are  to 
be  ascribed,  like  the  nervous  phenomena  of  tetanus,  to  a 
powerful  toxin.  Indeed,  the  properties  of  the  toxin  of 
B.  botulinus  have  been  studied  and  have  been  shown  to 
resemble  closely  the  toxins  of  tetanus  and  diphtheria 
with  respect  to  instability,  conditions  of  precipitation, 
etc.  An  antitoxin1  has  been  prepared  by  Kempner. 
It  has  the  power  of  neutralizing  the  toxin  and  has  con- 
siderable therapeutic  effect  when  given  a  short  time  after 
the  toxin. 

It  is  practically  very  important  to  realize  that  meat 
may  be  extensively  infected  with  the  B.  botulinus  and 
may  contain  relatively  large  quantities  of  the  toxins  with- 
out showing  the  ordinary  signs  of  decomposition.  We 


1  For  a  discussion  of  the  conditions  under  which  antitoxin 
formation  occurs  see  J.  Forssman,  "Studien  iiber  die  Antitoxin- 
bildung  bei  aktiver  Immunisierung  gegen  Botulismus,"  Cen- 
tralbl.  f.  Bakt.,  Orig.,  xxxviii,  p.  463,  1905. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      213 

have  therefore  in  B.  botulinus,  as  in  the  bacillus  of  teta- 
nus, an  example  of  strict  anaerobes  which  have  acquired 
the  ability  to  make  intense  poisons  but  have  apparently 
incidentally  lost  in  a  measure  the  common  putrefactive 
properties  ordinarily  possessed  by  spore-bearing  anae- 
robes. There  is  reason  to  think  that  isolated  cases  of 
botulism  are  not  extremely  rare  in  the  United  States. 
The  recognition  of  these  cases  by  purely  clinical  means 
may  be  very  difficult  when  the  typical  symptoms  are 
not  fully  developed.  In  foreign  countries,  where  meat 
is  distributed  by  a  different  system  from  that  prevailing 
in  the  United  States,  the  outbreaks  of  botulism  are  apt 
to  involve  many  people  in  one  locality,  whereas  in  our 
country  the  cases  are  apt  to  occur  in  small  numbers, 
owing  to  the  greater  opportunities  for  the  consumption 
of  portions  of  the  carcass  hi  different  localities. 


THE  FERMENTATIVE  AND  PUTREFACTIVE  PRO- 
CESSES FROM  THE  STANDPOINT  OF  THEIR 
PRODUCTS 

IT  is  helpful  to  review  the  fermentative  and  putrefac- 
tive processes  in  the  digestive  tract  of  man  from  the 
standpoint  of  their  products  although  such  a  course  may 
somewhat  temper  enthusiasm  by  revealing  our  ignorance 
in  many  important  directions.  I  shall  use  the  word 
"fermentative"  to  designate  the  decompositions  of  car- 
bohydrate and  fatty  substances  and  the  word  "putre- 
factive"  as  applied  to  the  cleavages  of  proteid  and  allied 
substances.  The  distinction  is  important,  for  while  the 
products  of  fermentation  are  in  themselves  usually 
unimportant  as  agents  of  intoxication,  the  products  of 
putrefaction  include  substances  containing  sulphur  or 
nitrogen  or  both  sulphur  and  nitrogen,  and  thus  frequently 
derive  a  chemical  basis  for  exerting  toxic  effects.  While 
making  this  distinction,  however,  I  do  not  lose  sight  of 
the  fact  that  fermentative  and  putrefactive  processes 
overlap  in  the  sense  that  they  furnish  some  products 
in  common,  such  as  carbon  dioxide  and  volatile  fatty 
acids ;  they  are  moreover  closely  linked  by  the  fact  that 
excessive  fermentation  in  the  digestive  tract  nearly 
always  leads  to  excessive  putrefaction,  for  reasons  which 
I  hope  to  make  clear. 

The  products  of  fermentative  decomposition  in  the 

214 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      215 

digestive  tract  may  be  dismissed  with  few  words.  The 
carbon  dioxide  which  results  from  the  breakdown  of 
sugars  is  of  interest  mainly  as  a  cause  of  gastric  flatu- 
lence or  small-intestinal  flatulence.  The  alcohol  formed 
is  probably  in  too  small  amount  to  be  toxically  significant 
even  when  fermentation  of  sugars  is  greatly  excessive. 
Of  the  acids  formed  we  have  to  think  of  lactic,  acetic, 
propionic,  and  butyric,  but  mainly  of  lactic  and  acetic. 
The  higher  volatile  fatty  acids  come  especially  from 
spore-bearing  anaerobes  (although  other  types  of  bacteria 
may  produce  them)  and  therefore  interest  us  also  as 
putrefactive  products.  All  these  acids,  however,  are 
irritants  by  virtue  of  their  acid  properties.  If  present 
in  considerable  concentration  in  a  healthy  digestive 
tract  or  in  more  moderate  concentration  in  the  tract  of  a 
person  with  an  irritable  stomach  or  small  intestine,  they 
may  be  efficient  factors  in  exciting  vomiting  or  diarrhoea. 
Nervous  disturbances  resulting  in  delayed  absorption 
may  be  responsible  for  the  accumulation  of  considerable 
acid  fluid  in  the  stomach  or  small  intestine.  There  is 
also  a  quite  different  aspect  to  the  excessive  production 
of  acid ;  namely,  the  withdrawal  of  excessive  amounts  of 
alkali  from  the  organism.  All  the  acids  mentioned  are 
readily  burned  in  the  body,  but  if  their  absorption  occurs 
with  uncommon  rapidity,  they  may  be  excreted  unburned 
and  combined  with  alkali.  This  robbing  of  the  organism 
-of  alkali  by  acid  is  under  some  conditions  a  grave  matter, 
leading  to  a  definite  form  of  intoxication,  but  probably 
the  acids  of  fermentative  origin  are  always  associated 
with  those  of  putrefactive  origin  in  bringing  about  this 


216      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

kind  of  intoxication,  where  this  is  of  digestive  rather 
than  of  metabolic  origin.  It  appears  to  me  very  ques- 
tionable whether  one  ever  meets  with  cases  of  marked 
acid  intoxication  referable  to  the  absorption  of  excessive 
quantities  of  organic  acids  formed  in  the  digestive 
tract,  but  there  is  some  reason  to  think  that  in  young 
children  a  moderate  degree  of  acidosis  sometimes  has 
its  main  origin  in  fermentative  disturbances  in  the 
intestine. 

Oxalic  Acid  and  Oxaluria.  —  It  is  now  well  established 
that  various  molds  and  bacteria  are  capable  of  acting 
upon  media  containing  sugar,  in  such  a  manner  as  to  give 
rise  to  the  formation  of  oxalic  acid.  The  thought  that 
considerable  quantities  of  oxalic  acid  may  arise  in  the 
digestive  tract  as  the  result  of  fermentative  decomposi- 
tion led  Baldwin  l  to  make  studies  with  a  view  to  learn- 
ing whether  oxaluria  can  be  experimentally  induced  in 
dogs  by  feeding  large  amounts  of  sugar  together  with 
food  (such  as  meat)  which  contains  no  oxalic  acid.  It 
was  found  in  these  experiments  that  oxaluria  was  not 
readily  induced  in  this  manner  in  healthy  dogs,  but  that 
prolonged  feeding  of  sugar  in  large  quantities  eventually 
led  to  a  state  of  oxaluria.  This  experimental  oxaluria 
was  associated  with  a  disturbance  of  function  in  the 
gastric  mucous  membrane  during  which  large  quantities 
of  mucus  were  formed.  The  contents  ob tamed  from 
the  stomach  under  these  conditions  failed  to  show  the 
presence  of  hydrochloric  acid.  It  seems  clear  that  the 

1  "An  Experimental  Study  of  Oxaluria,  with  Special  Reference 
to  its  Fermentative  Origin,"  Journ.  of  Exper.  Med.,  v,  p.  27, 1900. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      217 

oxaluria  and  the  accompanying  gastritis  were  referable 
to  pathological  fermentative  processes  induced  by  the 
excessive  feeding  with  sugar.  It  was  further  found  in 
these  experiments  that  there  had  been  a  production  of 
oxalic  acid  in  the  contents  of  the  stomach. 

It  was  further  noticed  in  the  experiments  just  men- 
tioned that  oxalic  acid  may  be  formed  in  a  medium 
containing  sugar  and  beef  extract,  when  this  me- 
dium is  inoculated  with  material  obtained  from  the 
stomach  of  human  patients  showing  a  marked  grade 
of  oxaluria. 

Whether  it  is  safe  to  conclude  from  the  foregoing  facts 
that  oxaluria  in  human  beings  ever  arises  from  the  fer- 
mentation of  carbohydrates  in  the  digestive  tract  is  not 
entirely  clear.  It  appears  probable  that  there  are  con- 
ditions of  carbohydrate  dyspepsia  in  which  not  incon- 
siderable quantities  of  oxalic  acid  are  formed  through 
fermentation  of  carbohydrates.  The  absorption  of  this 
oxalic  acid  would  necessarily  add  to  the  quantity 
which  must  be  burned  in  the  organism  in  order  to  keep 
the  excretion  of  oxalic  acid  within  normal  limits.  That 
excessive  excretion  of  oxalic  acid  by  the  urine  is  ever 
due  solely  to  the  production  of  oxalic  acid  in  the  digestive 
tract  appears  to  me  unlikely.  Modern  studies  indicate 
that  there  are  many  ways  in  which  oxalic  acid  can  be 
formed  in  the  organism,  and  the  greatest  significance 
that  can  be  claimed  for  the  oxalic  acid  produced  within 
the  digestive  tract  is  that  it  may  sometimes  be  formed 
in  such  amounts  as  to  make  it  one  factor  in  bringing 
about  a  pathological  condition  of  oxaluria.  Perhaps 


218      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

the  occurrence  of  carbohydrate  dyspepsia  which  is  so 
common  in  cases  of  oxaluria  may  influence  the  occur- 
rence of  oxaluria  in  an  indirect  manner  through  its 
effect  upon  proteid  metabolism,  but  of  such  an  influence 
we  at  present  know  nothing. 

Of  the  intermediate  stages  by  which  sugars  are  de- 
composed with  the  production  of  oxalic  acid  we  are  at 
present  in  ignorance,  but  there  is  some  reason  to  suspect 
that  glyoxylic  acid  forms  an  intermediate  product  of 
decomposition.  This,  however,  does  not  make  it  neces- 
sary to  assume  that  any  considerable  quantity  of  glyox- 
ylic acid  is  present  at  one  time. 

Propionic,  butyric,  and  higher  volatile  fatty  acids  are 
common  products  of  putrefaction.  They  are  formed 
by  putrefactive  anaerobes  not  merely  from  sugar-holding 
media,  but  from  proteid  media  in  which  there  is  no  free 
sugar,  although  carbohydrates  may  be  essential  to  ini- 
tiate decomposition.  Among  the  most  important  anae- 
robic bacteria  capable  of  forming  butyric  acid  during 
putrefaction  are  the  motile  organisms  known  as  the 
amylobacteria,  the  granulo-bacillus  immobilis  liquefaciens 
of  Grassberger  and  Schattenfroh  (probably  a  non-patho- 
genic form  of  B.  aerogenes  capsulatus) ,  the  bacillus  of 
symptomatic  anthrax  (rauschbrand),  the  bacillus  of 
malignant  oedema,  and  the  B.  putrificus  of  Bienstock 
(cadaver  bacillus). 

Acetone.  —  The  interesting  observation  has  been 
made  that  the  mixed  faecal  flora  growing  upon  a  peptone- 
bouillon  medium  for  a  period  of  a  week  at  the  body 
temperature  in  certain  instances  gives  rise  to  the  forma- 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      219 

tion  of  acetone.  This  appears,  however,  to  be  an 
exceptional  occurrence.  Up  to  the  present  time  it  has 
been  observed  only  in  the  case  of  material  derived 
from  two  individuals.  In  one  of  these  the  bacteria  with 
which  the  medium  was  inoculated  came  from  a  child 
suffering  from  well-marked  chronic  intestinal  putrefac- 
tion of  the  marantic  type  with  the  development  of  a  large 
abdomen. 

The  other  instance  in  which  the  flora  gave  rise  to  the 
formation  of  acetone  was  one  of  advanced  anaemia. 
Why  acetone  was  obtained  from  a  culture  in  dextrose 
bouillon  and  calcium  carbonate  but  not  in  dextrose 
bouillon  without  calcium  carbonate  was  not  clear.  The 
flora  from  this  case  also  gave  rise  to  the  production  of 
acetone  in  milk  to  which  calcium  carbonate  had  been 
added.  The  presence  of  sugar  is  not  necessary  to  the 
production  of  acetone  by  intestinal  flora,  as  is  shown 
by  the  fact  that  it  has  been  obtained  from  plain 
bouillon. 

It  is  not  at  present  clear  what  significance  should  be 
attached  to  the  ability  of  the  intestinal  bacteria  in  cer- 
tain cases  to  produce  acetone.  The  observations  here- 
tofore made  do  not  furnish  us  with  any  evidence  that 
acetone  is  ever  produced  in  the  human  organism  in  the 
intestinal  tract  through  the  activity  of  microorganisms. 
Nevertheless  the  finding  of  acetone  under  the  conditions 
just  mentioned  suggests  the  possibility  that  under  some 
conditions  this  ketone  may  be  produced  in  the  digestive 
tract.  I  do  not  know  of  any  observations  that  have 
heretofore  been  made  which  have  shown  the  formation 


220      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

of  acetone  by  intestinal  bacteria.  Schardinger1  found 
an  organism  which  he  called  B.  mascerans  which  gave  a 
mixture  of  acetone  and  alcohol  during  the  fermentation 
of  various  carbohydrates. 

An  organism  was  also  found  by  Br£audat 2  which  was 
able  to  produce  acetone  in  a  peptone  solution.  This 
bacterium  was  derived  from  the  drinking  water  of  a  town 
in  France,  which  came  from  a  subterranean  well.  It  was 
a  Gram-negative  facultative  aerobe  capable  of  liquefy- 
ing gelatin.  Under  certain  conditions  this  organism 
developed  spores.  On  potato  it  gave  rise  to  a  violet 
color.  The  organism  was  described  under  the  name  of 
B.  violarius  acetonicus. 

When  we  turn  to  the  consideration  of  the  nitrogen- 
holding  and  sulphur-holding  products  of  putrefactive 
cleavage,  the  scantiness  of  our  knowledge  comes  into  view 
with  almost  discouraging  clearness.  That  putrefactive 
processes  are  attended  by  the  formation  of  bases,  such 
as  ammonia,  amines,  diamines  (such  as  putrescin  and 
cadaverin),  cholin,  neurin,  sulphur  compounds,  and  va- 
rious aromatic  bodies,  has  been  known  many  years, 
and  something  has  been  learned,  though  by  no  means 
enough,  about  the  media  and  the  bacteria  which  deter- 
mine the  presence  and  proportions  of  these  substances. 
When,  however,  we  ask  ourselves  what  we  can  safely 
say  of  the  conditions  under  which  such  substances  arise 

1 "  Mitteilung  aus  der  staatlichen  Untersuchungsaustalt  fiir 
Lebensmittel,"  Wien.  klin.  Wochenschr.,  xvii,  p.  207,  1904. 

J"Sur  un  nouveau  microbe  producteur  d'acetone,"  Ann.  de 
Vlnst.  Pasteur,  xx,  p.  874,  1906. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      221 

in  the  human  intestine  and  of  their  pathological  effects, 
we  are  able  to  give  in  most  instances  only  very  inade- 
quate answers. 

BASIC   SUBSTANCES 

In  the  course  of  putrefaction  of  proteids  in  the 
intestine  ammonia  is  regularly  formed.  It  does  not 
appear,  however,  that  it  is  formed  in  quantities  or 
under  conditions  which  render  it  toxic  to  the  organ- 
ism, although,  as  elsewhere  stated,  it  is  possible  that 
ammonium  butyrate  acts  as  a  local  irritant.  The 
organism  is  well  adapted  to  care  for  moderate  quanti- 
ties of  ammonia,  which,  as  is  well  known,  is  united  with 
carbon  dioxide  in  the  liver  and  elsewhere  to  form  urea. 
The  splitting-off  of  ammonia  from  amino-acids  formed 
in  the  course  of  normal  digestion  is  a  physiological  pro- 
cess of  fundamental  importance  and  it  is  probably 
owing  to  the  physiological  arrangements  necessary  for 
the  disposal  of  ammonia  in  a  relatively  non-toxic  form 
that  the  organism  is  able  to  tolerate  the  digestion  of 
large  quantities  of  ammonia-forming  foods.  Likewise 
we  know  nothing  of  any  toxic  action  from  methylamin 
or  other  alkyl  amines.  It  has  been  supposed  that 
guanidin1  and  methyl  guanidin  sometimes  arise  in  the 
course  of  certain  kinds  of  putrefaction.  While  it  cannot 
be  denied  that  this  may  be  the  case,  we  have  at  present 
no  knowledge  that  it  is  the  case,  and  are  unable  to 
correlate  any  clinical  conditions  with  the  formation  and 

1  Kutcher  showed  that  guanidin  may  be  an  end-product  of 
prolonged  pancreatic  digestion.  He  found  the  base  in  the  arginin 
fraction. 


222      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

absorption  of  guanidin  or  methyl  guanidin.  Methyl 
guanidin  arises  from  the  oxidation  of  creatin  (or 
creatinin),  and  it  is  conceivable  that  under  some  con- 
ditions of  decomposition  of  meat  these  bodies  are  formed. 
Since,  however,  there  is  no  definite  evidence  on  this 
point  in  the  case  of  man,  I  shall  not  enter  into  a  discus- 
sion of  mere  possibilities. 

In  reference  to  the  bases  cholin  and  neurin  the  case  is 
somewhat  different.  Of  these  bases  neurin  is  much  more 
toxic  than  cholin,  its  action  being  directed  especially  to 
the  nervous  system.  That  cholin  is  toxic  when  absorbed 
from  the  intestinal  tract  is  not  wholly  clear  although  it 
is  well  known  that  the  subcutaneous  injection  of  cholin 
gives  rise  to  nervous  symptoms  and  a  decline  hi  blood 
pressure.  The  most  definite  results  that  have  been  ob- 
tained by  experimental  methods  in  respect  to  the  pro- 
duction of  cholin  are  those  of  Beattie  Nesbit.1  Nesbit 
started  from  the  fact  that  lecithin  may  be  decomposed 
with  a  yield  of  cholin.  It  has  been  assumed  by  Bocai 
that  lecithin  is  decomposed  during  the  process  of  diges- 
tion into  glycerophosphoric  acid  and  fatty  acids  and  cho- 
lin, and  that  these  products  are  individually  absorbed. 
This  view  suggests  that  it  might  be  dangerous  to  con- 
sume very  large  quantities  of  lecithin  as,  for  example,  in 
the  form  of  eggs,  as  cholin  cannot  be  regarded  as  a  wholly 
harmless  substance.  It  must  be  admitted,  however, 
that  there  is  evidence  to  support  the  idea  that  some 

1  "  On  the  Presence  of  Cholin  and  Neurin  in  the  Intestinal  Canal 
during  its  Complete  Obstruction.  A  Research  on  Autointoxi- 
cation," Journ.  Exper.  Med.,  iv,  p.  1,  1899. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT       223 

lecithin  may  be  absorbed  without  decomposition.1  It 
may  thus  be  a  matter  of  importance  to  the  organism 
whether  the  lecithin  introduced  into  the  digestive  tract 
is  split  through  the  decomposing  action  of  putrefactive 
bacteria  or  whether  it  undergoes  absorption.  The  mere 
quantity  of  lecithin  introduced  would  therefore  not  be  a 
measure  of  the  quantity  of  cholin  formed  and  absorbed. 
In  the  experiments  of  Nesbit  dogs  which  had  been  fed 
for  several  days  upon  the  yolks  of  eggs  were  subjected  to 
an  operation  in  which  a  ligature  was  placed  about  the 
small  intestine  just  above  the  ileocsecal  valve.  In  ex- 
periments of  this  sort  in  which  the  animal  lived  for  several 
days  after  operation  the  intestinal  contents  were  removed 
and  studied  for  the  presence  of  cholin.  On  the  basis  of 
various  reactions  for  cholin  chloride  it  was  determined 
that  the  intestinal  contents  of  the  animal  contained  this 
substance.  Some  evidence  also  was  obtained  to  indi- 
cate that  neurin  was  also  formed.  I  think  the  evidence 
on  this  point  is  not  quite  convincing.  Nesbit  also  found 
evidences  of  a  ptomaine  associated  with  cholin  and 
neurin,  the  chemical  nature  of  which  was  left  in  doubt. 
These  observations  render  it  probable  that,  provided  the 
intestine  contains  any  considerable  quantity  of  lecithin, 
cholin,  neurin,  and  perhaps  other  bases  are  formed  as  a 
result  of  intestinal  obstruction.  It  must  be  stated,  nev- 
ertheless, that  Nesbit  failed  to  obtain  definite  evidence 
that  the  bases  found  by  him  in  the  intestinal  canal  of  the 
dog  were  really  toxic.  It  is  clear  that  much  more  work 

1  P.  von  Walter,  "Zur  Lehre  von  der  Fettresorption,"  Archiv 
f.  Anat.  u.  Physiol,  Physiol.  Abt.,  p.  329,  1890. 


224      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

needs  to  be  done  before  the  relation  of  cholin  and  neurin 
to  intoxications  from  the  digestive  tract  is  placed  on  a 
satisfactory  basis. 

There  are  some  instances  of  a  remarkable  idiosyncrasy 
on  the  part  of  certain  persons  toward  eggs.  I  recall  a 
child  in  whom  the  taking  of  an  egg  was  regularly  fol- 
lowed by  prostration  and  slight  fever  and  headache. 
Whether  such  phenomena  as  these  bear  any  relation  to 
the  formation  of  cholin  or  neurin  is  of  course  an  open 
question. 

Putrescin  and  Cadaverin.  —  Putrescin  (tetramethyl- 
endiamin)  and  cadaverin  (pentamethylendiamin)  are 
products  of  proteid  decomposition  which  are  formed  at 
times  in  the  human  intestine  under  conditions  at  present 
obscure.  It  seems  not  improbable  that  peculiar  states 
of  bacterial  activity  may  have  an  influence  on  the  pro- 
duction of  these  bases,  and  it  is  very  desirable  that  the 
bacterial  flora  should  be  studied  with  great  care  in  those 
cases  of  cystinuria  in  which  putrescin  and  cadaverin  can 
be  obtained  from  the  intestinal  contents.  According 
to  Brieger  *  the  peculiar  odor  of  cholera  stools  is  due 
principally  to  pentamethylendiamin,  but  strict  proof 
of  this  has  not  yet  been  furnished. 

Baumann  and  Udranzky2  found  about  0.5  gram  per 

1  Brieger  and  Stadthagen,  "Ueber  Cystinurie,"  Berl.  klin.  Wo- 
chenschr.,  xxvi,  p.  344,  1889. 

2  "Das   Benzoylchlorid   als   Reagens,"  Bericht.  d.  Chem.  Ge- 
sellsch.,  xxi,  p.  2744,  1888;  "Ueber  die  Identitat  des  Putrescins 
und  des   Tetramethylendiamin,"   ibid.,   p.   2938;     "Ueber    das 
Vorkommen  von  Diaminen  sogenannten  Ptomainen  bei  Cystinu- 
rie," Zeitschr.  f.  physiol  Chem.,  xiii,  p.  562,  1899. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      225 

day  of  diamines  (principally  tetramethylendiamin)  in 
the  faeces  of  a  cystinuria  patient.  This  quantity  is 
equal  to  the  amounts  found  in  the  urine  from  the  same 
case.  In  the  urine,  however,  the  cadaverin  constituted 
about  sixty  per  cent,  of  the  diamines ;  in  the  faeces  only 
from  ten  to  fifteen  per  cent,  of  the  bases  consisted  of 
cadaverin.  Neither  Brieger  nor  Baumann  and  Udranzky 
was  able  to  find  diamines  in  normal  fasces.  Moreover, 
Baumann  and  Udranzky  were  not  able  to  find  these 
bases  in  examples  of  disease  other  than  cystinuria. 
Roos l  in  a  case  of  combined  malaria  and  dysentery  with 
fever  and  enlargement  of  the  spleen  found  in  the  faeces 
a  small  quantity  of  pentamethylendiamin.  There  was 
very  little  indican  in  the  urine  of  this  patient.  He  was 
unable  to  find  diamines  in  cases  of  malaria  alone.  In  a 
case  of  fever  following  gonorrhoea  he  was  able  to  obtain 
small  quantities  of  dibenzoylcadaverin. 

Although  the  study  of  the  conditions  under  which 
putrescin  and  cadaverin  are  formed  in  the  intestinal 
tract  is  of  much  biological  interest,  there  is  at  the  present 
time  little  evidence  that  these  diamines  are  ever  formed 
in  sufficient  quantities  in  the  human  intestine  to  con- 
stitute in  themselves  factors  in  the  production  of  states 
of  intoxication.  The  association  with  cystinuria  is  a 
striking  fact,  and  the  further  investigation  of  this  disease 
will  doubtless  give  us  an  explanation  of  the  relationship 
between  the  production  of  diamines  and  the  formation 
of  cystin,  if  indeed  there  be  any  necessary  relation. 

1"Ueber  das  Vorkommen  von  Diaminen  bei  Krankheiten," 
Zeitschr.  f.  physiol.  Chem.t  xvi,  p.  192,  1892. 

q 


226      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

Ellinger  J  found  that  putrescin  may  be  obtained  from 
the  bacterial  decomposition  of  ornithin.  He  found  also 
that  cadaverin  results  from  the  decomposition  of  lysin. 
Under  the  designation  " ptomaines"  Selmi  2  described  a 
number  of  basic  substances  resembling  plant  alkaloids 
in  their  reactions  and  liable  to  be  mistaken  for  morphine, 
conine,  etc.  He  obtained  them  from  cadavers.  That 
such  bodies  are  sometimes  formed  in  the  human  digestive 
tract  appears  likely,  but  has  not  been  satisfactorily 
established.  In  fact,  the  " ptomaines"  are  in  most  in- 
stances not  so  clearly  defined  in  their  chemical  characters 
as  could  be  desired.  Moreover,  their  pharmacological 
characters  are  also  insufficiently  definite.  For  these 
reasons  any  discussion  of  these  bodies  in  the  present 
connection  would  be  purely  academic. 

SULPHUR   COMPOUNDS 

Mercaptan.  —  The  sulphur  compounds  resulting  from 
putrefactive  decomposition  in  the  intestine  have  re- 
ceived little  attention  from  the  standpoint  of  their 
pharmacological  action.  It  is  therefore  difficult  at 
present  to  form  a  just  estimate  of  their  importance  for 
intestinal  intoxications.  It  was  claimed  by  Nencki 
that  methyl  mercaptan  is  one  of  the  gases  formed  in  the 
intestine  during  putrefaction.  He  based  this  contention 
on  a  study  of  the  faeces,  but  did  not  take  the  precaution 
to  examine  the  material  promptly  after  collection. 

1  "Die  Constitution  des  Ornithins  und  des  Lysins,"  Zeitschr.  f. 
physiol.  Chem.,  xxix,  p.  334,  1900. 

2"Sulle  ptomaine  ed  alcaloidi  cadaverici  e  lore  imputanza  in 
toxicogia,"  Bericht.  d.  deutsch.  chem.  Gesellsch,,  ii,  p.  808,  1878. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      227 

It  appears  to  me,  therefore,  not  clear  that  the  methyl 
mercaptan  found  by  Nencki  was  not  formed  during 
putrefaction  outside  the  body.  My  scepticism  on  this 
point  rests  partly  on  the  fact  that  although  I  have 
made  many  examinations  of  the  fresh  faeces  from  per- 
sons with  excessive  intestinal  putrefaction,  I  have  never 
been  able  to  find  methyl  mercaptan  by  means  of  the 
isatin-sulphuric-acid  reaction.  It  appears  improbable 
that  methyl  mercaptan  is  produced  in  the  human  large 
intestine  in  the  course  of  ordinary  putrefactive  troubles, 
although  it  must  be  admitted  that  it  may  perhaps  arise 
under  some  exceptional  conditions.  It  may  be  stated 
before  leaving  the  subject  of  mercaptan  that  experi- 
ments were  made  upon  dogs  and  monkeys  in  which  ethyl 
mercaptan  in  a  solution  of  one  part  in  one  thousand 
parts  of  water  failed,  when  injected  into  the  large 
intestine,  to  give  rise  to  definite  evidence  of  intoxica- 
tion unless  very  large  quantities  were  employed.  Thus 
during  a  period  of  ten  days  a  dog  of  medium  size  re- 
ceived 20, 30, 50, 56,  110,  110,  110,  and  110  c.c.  of  such  a 
solution  on  successive  days  without  exhibiting  symp- 
toms. The  injection  of  50  c.c.  of  a  solution  two  and  one- 
half  parts  per  one  thousand  parts  was  not  well  retained. 
It  was  only  when  a  dose  of  120  c.c.  of  this  concentration 
was  introduced  into  the  stomach  that  vomiting  occurred. 
The  rectal  injection  of  an  ethyl  mercaptan  solution  of 
1 : 1000  strength  in  quantities  of  10  to  30  c.c.  daily  in  a 
medium-sized  monkey  failed  to  give  rise  to  symptoms. 

Hydrogen  Sulphide.  —  There  is  reason  for  thinking  that 
the  production  of  hydrogen  sulphide  in  the  digestive 


228      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

tract  is  of  more  importance  to  the  organism  than  the 
formation  of  mercaptan.  That  this  gas  is  regularly 
formed  in  at  least  moderate  quantities  under  normal 
conditions  is  apparent  from  the  fact  that  the  intestinal 
contents  are  rendered  dark  in  color  after  the  administra- 
tion of  iron  salts  owing  to  the  formation  of  sulphide  of 
iron.  This  occurs,  as  is  well  known,  in  well  persons. 
Moreover,  the  presence  of  hydrogen  sulphide  in  the 
freshly  voided  fseces  can  be  readily  demonstrated.  It 
is  also  true  that  the  mixed  faecal  flora  from  the  human 
intestine,  both  in  health  and  disease,  is  capable  of 
producing  hydrogen  sulphide  upon  a  medium  containing 
proteid  that  has  been  partially  hydrolyzed.  This  is 
true,  for  example,  of  the  growths  upon  bouillon. 
Hydrogen  sulphide  is  produced  early  in  the  course  of 
putrefaction,  and  its  presence  in  flasks  containing 
peptone  bouillon  inoculated  with  f  secal  flora  is  regularly 
demonstrable  within  the  first  twenty-four  hours.  It  is 
difficult  to  form  a  judgment  as  to  how  much  hydrogen 
sulphide  is  produced  through  intestinal  putrefaction  in 
the  course  of  a  given  period  or  how  much  is  absorbed. 
Assuming  that  the  production  is  the  same  in  a  given 
series  of  individuals,  it  is  highly  probable  that  the  ab- 
sorption would  be  variable,  and  it  is  of  course  upon  the 
absorption  of  the  gas  that  its  importance  to  the  organism 
chiefly  depends. 

It  seems  probable  that  in  health  the  formation  of 
hydrogen  sulphide  is  limited  to  the  large  intestine  and 
perhaps  a  short  extent  of  the  adjoining  small  intestine. 
Under  pathological  conditions,  hydrogen  sulphide  is 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      229 

formed  in  other  parts  of  the  digestive  tract.  There  are 
cases  of  dilatation  of  the  stomach  from  which  one  may 
remove  material  which  is  undergoing  putrefaction  with 
the  formation  of  hydrogen  sulphide.  The  production 
of  hydrogen  sulphide  in  this  situation  is  certainly  to  be 
regarded  as  pathological.  I  am  not  clear,  however,  that 
it  points  to  the  presence  of  pathological  bacteria,  for 
it  is  easy  to  show  that  typical  organisms  of  the  B.  lactis 
aerogenes  type  are  able  to  form  hydrogen  sulphide  when 
growing  in  bouillon  containing  cystin.  Cystin  is  a  decom- 
position product  of  proteids,  and  it  is  conceivable  that  in 
a  stagnant  stomach  proteid  digestion  may  go  on  to  the 
formation  of  cystin  among  the  cleavage  products  and  that 
this  is  then  decomposed  through  the  action  of  B.  lactis 
aerogenes.  The  ability  to  form  hydrogen  sulphide  from 
cystin  is  widespread  among  bacteria.  The  colon  bacilli 
liberate  it  abundantly  when  growing  in  a  cystin  medium.1 

Among  persons  who  take  organic  iron  it  is  usual  to 
note,  after  a  little  time,  a  dark  brown  color  on  the  tongue 
which  appears  to  be  dependent  on  the  formation  of  iron 
sulphide  in  this  situation.  The  sulphide  production 
is  referable,  doubtless,  to  the  formation  of  hydrogen 
sulphide,  but  the  conditions  of  its  production  are  not 
I  known.  It  does  not  appear  that  the  blackening  of  the 
,  tongue  after  taking  iron  can  be  regarded  as  pathological, 
|as  it  may  be  observed  in  persons  apparently  free  from 
i  disorders  of  digestion. 

I  have  made  some  observations  to  determine  at  what 

1  This  is  true  also  of  the  bacilli  of  dysentery  and  of  typhoid 
fever. 


230      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

level  of  the  digestive  tract  one  finds  bacteria  capable 
of  forming  hydrogen  sulphide  when  grown  in  peptone 
bouillon.  These  observations  were  made  upon  the 
digestive  tract  of  infants.  The  mixed  flora  from 
various  portions  of  the  large  intestine  and  lower  part  of 
the  ileum  regularly  gave  hydrogen  sulphide.  Where  the 
inoculated  material  was  derived  from  children  dying 
of  pneumonia  or  some  condition  unconnected  with  de- 
rangements of  digestion,  it  was  unusual  to  obtain  hydro- 
gen sulphide  from  bacteria  derived  from  portions  of  the 
tract  lying  above  the  lower  part  of  the  ileum.  It  was 
frequently  noted,  however,  in  children  dying  from 
marasmus  that  the  flora  obtained  from  the  stomach  and 
from  portions  of  the  small  intestine  above  the  ileum 
gave  hydrogen  sulphide  when  grown  on  peptone  bouillon. 
In  some  instances  it  was  observed  that  more  hydrogen 
sulphide  was  formed  from  the  bacteria  derived  from  the 
stomach  of  such  children  than  from  the  bacteria  obtained 
from  the  rectum. 

We  have  at  present  very  little  satisfactory  knowledge 
of  the  influence  of  hydrogen  sulphide  upon  the  organism 
in  cases  where  the  gas  is  liberated  in  the  intestine.  Fre- 
quent reference  is  made  in  works  dealing  with  auto- 
intoxications to  a  publication  by  Senator,1  concerning 
what  he  regarded  as  a  case  of  pure  hydrothionsemia. 
The  patient  in  this  instance  was  a  man  supposed  to  have 
been  well  previously  and  who  after  an  error  in  diet  be- 

iaUeber  einen  Fall  von  Hydrothionamie  und  iiber  Selbstin- 
fection  durch  abnorme  Verdauungsvorgange,"  BerL  klin.  Wochen- 
schr.,  v,  p.  254,  1868. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      231 

came  ill  with  a  gastro-enteric  catarrh,  presumably  located 
mainly  in  the  caecum.  On  the  third  day  after  the  illness 
there  suddenly  occurred  a  severe  seizure  of  vomiting 
accompanied  with  an  intense  odor  of  hydrogen  sulphide. 
Simultaneously  the  patient  suffered  from  dizziness  and 
a  little  later  passed  into  a  state  of  collapse  without 
loss  of  consciousness,  the  eruction  of  gas  continuing  mean- 
time. The  first  urine  passed  gave  a  definite  reaction  for 
hydrogen  sulphide.  On  the  following  day  the  patient 
recovered.  Other  somewhat  similar  instances  have  been 
described  by  Betz,1  Stefanio,  and  Emminghaus.2  Among 
the  symptoms  that  have  been  met  with  in  such  cases 
there  have  been  prominent  those  pointing  to  disordered 
function  of  the  central  nervous  system,  including  head- 
ache, dizziness,  delirium,  mental  depression,  drowsiness, 
stupor,  and  collapse.  Somewhat  similar  manifestations 
have  been  observed  in  experimental  poisoning  by 
hydrogen  sulphide  in  animals  and  men.3  The  nervous 
symptoms  observed  under  these  conditions  have  fre- 
quently been  more  severe  than  those  arising  in  sponta- 
neous hydrothionsemia,  probably  because  the  quantity 
of  gas  absorbed  is  greater  in  the  former  cases.  Appar- 
ently somewhat  at  variance  with  the  results  of  poisoning 
in  dogs  is  the  statement  that  many  persons  subjected 

lUUeber  Hydro thionammoniaemie, "  Memorabilien,  Ix,  p.  145, 
1864. 

2"Zwei  Falle  von  mehrfacher  Perforation  des  Verdauungs- 
kanals  und  H2S-Gehalt  im  Urin,"  Berl.  klin.  Wochenschr.,  ix,  pp. 
477  and  491,  1872. 

3  See  especially  K.  B.  Lehmann,  "  Experimentalle  Studie  liber 
den  Einfluss  technisch  und  hygienisch  wichtiger  Gase  und  Dampfe 
auf  den  Organismus,"  Archiv  /.  Hyg.,  xiv,  p.  135,  1892. 


232      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

to  the  Burgeon  treatment  for  pulmonary  phthisis  have 
been  able  to  take  considerable  quantities  of  hydrogen 
sulphide  administered  by  the  rectum  without  injurious 
effects.  It  appears  to  me  extremely  doubtful,  however, 
from  the  results  of  experiments  made  upon  dogs  whether 
it  is  really  possible  to  bring  about  the  rapid  absorption 
of  more  than  small  quantities  of  hydrogen  sulphide  in 
man  without  giving  rise  to  collapse.  In  experiments 
conducted  on  dogs  it  is  necessary  to  use  the  utmost 
caution  in  administering  the  gas  by  the  rectum  in  order  to 
prevent  fatal  collapse.  Nevertheless,  small  quantities 
of  the  gas  may  almost  certainly  be  absorbed  from  the 
human  intestine  without  giving  rise  to  noticeable  dis- 
turbance of  nervous  function  or  to  the  presence  of 
hydrogen  sulphide  in  the  urine.  Friedrich  Miiller  * 
showed  that  in  various  disorders  of  the  intestine  hydrogen 
sulphide  is  liberated  in  the  lungs,  but  without  simulta- 
neous appearance  of  hydrogen  sulphide  in  the  urine, 
owing  probably  to  the  small  quantity  of  gas  formed. 
In  some  cases  of  extreme  dilatation  of  the  stomach  the 
formation  of  hydrogen  sulphide  is  so  abundant  as  to 
make  it  seem  strange  that  the  patients  escape  without 
symptoms  of  intoxication.  Their  immunity  in  these 
cases  appears  to  depend  on  the  fact  that  there  is  an  enac- 
tion of  the  gas  when  it  accumulates  in  considerable 
volume. 

It  has  come  to  be  well  recognized  that  local  inflam- 
matory conditions  of  the  bladder  may  be  associated  with 

'"Ueber  Schwefelwasserstoff  im  Ham,"  Berl.   klin.  Wochen- 
schr.,  xxiv.,  p.  405,  1887. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      233 

a  putrefaction  of  proteid  material  with  liberation  of 
hydrogen  sulphide.  This  condition  is,  of  course,  one 
quite  distinct  from  true  hydrothionsemia,  and  it  runs 
its  course  without  symptoms  of  general  intoxication. 

The  toxic  character  of  hydrogen  sulphide  for  dogs  is 
plainly  seen  from  a  typical  record  of  experiments  in 
which  a  saturated  aqueous  solution  of  hydrogen  sulphide 
was  introduced  into  the  rectum.  Fifteen  cubic  centi- 
meters of  such  a  saturated  solution  were  introduced 
daily  into  the  rectum  of  a  dog  weighing  sixteen  and  one- 
half  pounds.  No  effects  were  observed.  After  one 
week  the  volume  of  the  enema  was  increased  to  thirty 
cubic  centimeters.  After  a  daily  administration  of  this 
amount  during  two  weeks,  the  volume  was  increased  to 
forty-five  cubic  centimeters.  The  animal  immediately 
passed  into  a  state  of  collapse.  It  was  found  that  by 
injecting  forty-five  cubic  centimeters  very  slowly  the 
enema  was  tolerated,  although  it  gave  rise  to  prostration. 
After  a  period  of  five  days,  in  which  this  quantity  was 
daily  administered,  the  volume  was  increased  to  sixty 
cubic  centimeters,  but  with  the  result  of  bringing  on 
collapse  which  proved  nearly  fatal.  The  volume  of  the 
enema  was  then  reduced  to  thirty  cubic  centimeters. 
After  a  few  days  it  became  necessary  to  discontinue 
the  injections  of  hydrogen  sulphide,  as  the  dog  failed 
to  eat.  The  nutrition  of  the  animal  suffered  in  the 
course  of  these  infections.  There  appeared  to  be  a 
slight  reduction  in  haemoglobin  in  the  course  of  the 
experiment.  A  pronounced  ansemia  was,  however,  not 
induced. 


234      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

Hydrogen  Sulphide  and  its  Relation  to  Enterogenic 
Cyanosis.  —  In  1902  Stokvis 1  described  a  peculiar  and 
apparently  new  clinical  state  under  the  name  of  "  auto- 
toxic  enterogenic  cyanosis."  His  observation  had  refer- 
ence to  a  man  fifty-eight  years  of  age  who  suffered  from 
a  severe  enteritis  associated  with  pronounced  cyanosis 
of  the  skin  and  visible  mucous  membranes,  together  with 
a  slight  swelling  of  the  terminal  phalanges.  On  making 
a  spectroscopic  examination  of  the  skin  and  mucous 
membranes  of  his  patient,  Stokvis  was  easily  able  to 
make  out  in  addition  to  the  two  feeble  oxyhsemoglobin 
bands  a  small  absorption  band  in  the  red,  corresponding 
to  the  absorption  spectrum  of  methsemoglobin.  It  is 
of  course  well  known  that  the  experimental  methse- 
moglobinuria  which  may  be  induced  by  a  variety  of 
poisons,  such  as  potassium  chlorate,  nitrobenzol,  and 
various  derivatives  of  anilin,  gives  rise  to  a  characteristic 
cyanosis  of  the  skin  and  mucous  membranes.  Stokvis 
was  therefore  inclined  to  believe  that  the  cyanotic 
discoloration  of  the  skin  of  his  patient  could  be  ascribed 
to  the  methsemoglobin  present  in  the  blood.  He  assumed 
that  some  poisonous  substances  had  been  formed  in  the 
intestine  which  gave  rise  to  a  transformation  of  a  portion 
of  the  haemoglobin  into  methsemoglobin.  Three  similar 
cases  were  soon  after  reported  by  Talma,2  who  reached 
the  same  conclusions  as  Stokvis ;  namely,  that  the  methse- 

1  "  Zur   Casuistik    der    autotoxischen    enterogenen    Cyanosen 
.(Methaemoglobinaemia  (?)  et  enteritis  parasitaria),"  Festschr.  f.  v. 
Leyden,  i,  p.  597,  1902. 

2  Tijdschrift  voor  Geneesk.,  ii,  p.  721,  1902. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      235 

moglobin  observed  in  his  cases  was  the  result  of  intoxi- 
cation through  the  intestinal  tract,  due  to  poisonous 
substances  formed  there.  In  1905  Hi j mans  van  der 
Bergh l  reported  two  cases  of  enterogenic  cyanosis  which 
at  first  sight  appeared  to  have  the  same  pathological 
basis  as  those  reported  by  Stokvis  and  Talma.  He  found, 
however,  on  careful  investigation  that  the  substance 
contained  in  the  blood  of  one  of  his  patients  could  not 
have  been  methaemoglobin.2  The  absorption  spectra 
observed  by  him  showed  the  closest  similarity  to  the 
spectrum  of  sulphhsemoglobin.  Attempts  were  made  to 
determine  the  presence  of  hydrogen  sulphide  or  rather 
of  sulphhsemoglobin  in  the  blood,  but  these  were  not 
wholly  successful,  although  he  was  able  by  means  of  the 
Caro-Fischer  reagent  (a  solution  of  pure  amidodimeth- 
ylanilin  with  ferric  chloride)  to  obtain  a  blue  color 
due  to  the  formation  of  methylene  blue  and  indicative 
of  the  presence  of  hydrogen  sulphide.  Van  der  Bergh 
concludes  that  his  patient  suffered  from  the  passage  of 
hydrogen  sulphide  into  the  blood  from  the  intestine.3 

lf'Enterogene    Cyanose,"    Deutsch.    Archive    /.    Tdin.    Med., 
Ixxxiii,  p.  86,  1905. 

2  This  writer  has  lately  reported  one  instance  of  enterogenic 
cyanosis  associated  with  methaemoglobinsemia,  in  which  the  blood 
was  shown  to   contain  nitrites.      This    observation    appears  of 
much  importance  for  the  doctrine  of  intestinal  intoxication,  as  it 
is  well  established  that  nitrites  readily  cause  methaemoglobinsemia 
under  experimental   conditions.      A.  A.  Hymans  van  der  Bergh 
und  A.  Grutterink,  "  Enterogene  Cyanose,"   Zweite  Mittheilung, 
Berl.  klin.  Wochenschr.,  No.  1,  p.  7,  1906. 

3  Several  of  these  cases  of  sulphhsemoglobinsemia  have  been 
associated  with  obstinate  constipation,  the  relief  of  which  has  been 
followed  by  rapid  improvement  in  the  blood  state. 


236      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

The  clinical  conditions  present  in  one  of  Van  der 
Bergh's  cases  of  enterogenic  cyanosis  deserve  mention. 
This  case  was  a  child  nine  years  of  age  in  which  there  were 
marked  digestive  disturbances  with  diarrhoea.  It  had 
been  observed  by  the  mother  that  the  child  passed  very 
little  urine.  This  anuria  was  probably  owing  to  the 
constant  diarrhoea.  For  two  years  the  mother  had  ob- 
served that  her  child  readily  became  bluish  on  slight 
excitement.  This  condition  gradually  became  more 
pronounced,  and  finally  the  child  grew  very  cyanotic 
even  when  at  rest.  The  ends  of  the  fingers  were  also 
somewhat  clubbed.  When  the  child  was  three  or  four 
years  of  age  the  abdomen  became  much  distended  and 
this  distension  gradually  increased.  There  was  no  evi- 
dence whatever  of  any  cardiac  affection.  The  urine  was 
very  much  reduced  in  amount  and  contained  no  albumin 
and  no  sugar,  but  is  said  to  have  contained  a  little  indol. 
The  sediment  contained  many  bacteria,  leucocytes,  and 
calcium  oxylate.  The  movements  were  very  thin,  had 
a  strongly  alkaline  reaction,  and  smelled  of  ammonia. 
The  movements  were  sometimes  yellow,  sometimes  dark 
brown  or  nearly  black,  and  always  became  very  dark  on 
standing  in  the  air.  No  protozoa  were  found.  The 
author  states  that  a  fistula  existed  between  the  bladder 
and  rectum,  and  this  was  probably  the  cause  of  the  indol 
found  in  the  urine.  The  child  was  not  anaemic.  An 
endeavor  was  made  to  control  the  cystitis  by  means  of 
urotropin  and  the  proteid  food  was  greatly  reduced  in 
order  to  diminish  the  hydrogen  sulphide  formed  in  the 
intestine.  This  resulted  in  the  disappearance  of  indol 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      237 

from  the  urine.  The  development  of  hydrogen  sulphide 
in  the  urine,  however,  could  not  be  wholly  checked.  After 
a  time,  nevertheless,  there  was  distinct  improvement. 
The  size  of  the  abdomen  became  reduced  and,  strikingly 
enough,  the  blue  color  of  the  skin  and  mucous  membranes 
in  the  course  of  a  few  weeks  became  much  less  marked 
and  ultimately  scarcely  any  cyanosis  could  be  detected. 
Nevertheless  by  spectroscopic  examination  the  charac- 
teristic sulphhsemoglobin  band  in  the  spectrum  remained 
visible  although  apparently  somewhat  weakened. 

AROMATIC   PRODUCTS   OF   PUTREFACTIVE   DECOMPOSITION 

Phenol  and  Cresol.  —  Among  the  aromatic  products 
of  putrefaction  are  the  phenols.  In  health  the  intestinal 
contents  contain  only  small  quantities  of  these  sub- 
stances. In  some  pathological  conditions  attended  by 
excessive  putrefaction  in  the  intestine  they  are  found  in 
the  intestinal  contents  in  amounts  considerably  above 
the  normal  amount,  which  is  always  small.  The  quan- 
tities found  are,  however,  never  large  —  never  so  large, 
for  example,  as  in  the  case  of  indol.  What  are  the  con- 
ditions of  bacterial  decomposition  which  lead  to  this 
production  of  phenol  it  is  at  present  impossible  to  state 
with  confidence.  Phenol  is  doubtless  derived  from  the 
breaking-down  of  tyrosin,  and  it  is  therefore  in  decom- 
positions in  which  tyrosin-containing  foodstuffs  are  in- 
volved that  we  would  expect  to  find  the  phenols  in 
greatest  amount.  I  am  not  able  to  say  whether  the  facts 
of  experience  correspond  to  this  view.  Of  the  common 
proteid  foods,  milk  is  one  which  yields  considerable 


238      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

quantities  of  tyrosin  from  its  casein  (the  yield  reaching 
as  high  as  four  and  one-half  per  cent.).1  Phenol  is  paired 
in  the  body,  as  is  well  known,  with  sulphuric  acid  and  is 
excreted  as  phenol-potassium-sulphate. 

Although  the  quantity  of  phenol  found  in  the  fa?ces 
at  any  one  time  is  small,  the  quantity  excreted  in  twenty- 
four  hours  in  the  urine  may  be  fairly  high.  Cresols  are 
included  with  phenol  in  these  estimates.  The  reason 
for  this  considerable  excretion  is  in  part  the  fact  that 
phenols  are  produced  in  the  organism  in  the  course  of  the 
metabolism  of  normal  cells.  The  quantity  thus  formed 
is,  however,  small,  and  the  excess  above  this  amount 
which  we  find  in  certain  putrefactive  cases  may  there- 
fore be  properly  attributed  to  the  phenols  produced  by 
putrefaction  in  the  intestine.  I  have  found  the  highest 
values  for  phenols  in  the  urine  in  cases  of  chronic  intes- 
tinal indigestion  characterized  by  marasmus  and  disten- 
sion of  the  abdomen  in  children. 

It  does  not  appear  that  the  phenols  can  be  regarded  as 
important  toxic  agents,  since  the  maximal  quantities 
which  we  find  in  the  urine  in  cases  of  disease  may  be 
considerably  exceeded  during  the  prolonged  therapeutic 
administration  of  phenols  without  giving  rise  to  any 
symptoms  whatever.  Nevertheless,  it  is  likely  that  the 
continued  absorption  of  moderate  quantities  of  phenols 

1  Among  other  substances  which  have  been  found  to  yield 
relatively  large  proportions  of  tyrosin  are  fibrin,  3.82  per  cent.; 
zein  from  corn,  10.06  per  cent.;  glutenfibrin,  4.43  per  cent.;  con- 
glutin  from  the  seeds  of  lupins,  3.2  per  cent.;  horn,  4.58  per  cent.; 
histone  from  thymus,  6.31  per  cent.;  protamin  of  .the  seehare,  8.4 
per  cent. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      239 

from  the  intestine  over  a  long  period  of  time  may  prove 
injurious  to  the  cells  of  the  liver  and  to  other  cells  con- 
cerned with  the  pairing  of  phenol  to  phenol-sulphuric 
acid.  This  deleterious  effect  is  probably  of  greater 
importance  in  persons  in  whom  the  cell  protoplasm  of 
the  liver  has  been  somewhat  damaged  than  in  the  case 
of  normal  persons. 

Skatol.  —  This  substance  is  formed  in  very  small 
quantities  from  day  to  day  in  some  normal  persons,  and 
in  persons  suffering  from  excessive  intestinal  putrefac- 
tion it  may  be  formed  in  larger  quantities  than  is  nor- 
mally the  case.  As  compared  with  the  quantity  of  indol 
found  in  the  intestinal  tract,  the  quantity  of  skatol  is 
almost  always  small.  I  have  occasionally  met  with  in- 
stances in  which  the  f seces  contain  relatively  large  quan- 
tities of  skatol,  eight  to  ten  milligrams  in  one  hundred 
grams  of  fresh  material.  This  has  occurred  only  in 
persons  with  marked  signs  of  intestinal  or  nervous  dis- 
order. Very  rarely  I  have  observed  much  skatol  in  the 
intestinal  contents  with  only  a  mere  trace  of  indol.1 

Like  indol,  skatol  is  derived  from  tryptophan,  but 
what  are  the  conditions  that  determine  its  formation 
rather  than  the  formation  of  indol  we  do  not  at  present 
know.  I  have  given  this  subject  considerable  attention, 
but  without  being  able  to  determine  the  bacteria  con- 

1  The  most  extreme  instance  of  this  sort  was  observed  in  a 
patient  suffering  from  multiple  neuritis  and  the  psychosis  charac- 
teristic of  alcoholic  intoxication.  As  this  patient  had  not  taken 
alcohol,  the  nervous  condition  was  attributed  to  an  obscure  type 
of  intestinal  intoxication.  A  study  of  the  urine  and  faeces  gave 
some  ground  for  this  suspicion. 


240      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

cerned  in  the  formation  of  skatol  rather  than  indol. 
Suspicion  rests  on  a  slender,  curved,  Gram-positive  organ- 
ism about  four  microns  in  length  which  I  have  several 
times  found  associated  with  the  production  of  skatol, 
but  which  has  not  yet  been  obtained  in  pure  culture.1 

I  found  that  the  administration  of  skatol  to  monkeys 
by  the  mouth  and  by  subcutaneous  injections  has  been 
followed  by  the  appearance  of  a  substance  in  the  urine 
giving  the  Ehrlich  dimethylamidobenzaldehyde  reaction 
of  the  urine,  and  the  administration  of  0.1  gm.  of  skatol 
to  man  has  been  followed  by  the  appearance  of  a  stronger 
Ehrlich  reaction  than  was  previously  present.2  I  am 
inclined  therefore  to  ascribe  the  intensification  of  the 
reaction  in  these  cases  to  the  administration  of  skatol. 
The  direct  evidence,  however,  is  lacking  to  show  that 
the  reaction  thus  induced  or  accentuated  is  dependent 
on  the  presence  of  the  same  substance  in  the  urine  that 
gives  rise  ordinarily  to  the  Ehrlich  aldehyde  reaction. 

1  The  ground  for  this  suspicion  is  that  flasks  containing  pu- 
trefactive media  inoculated  with  faecal  bacteria  have  shown  the 
presence  of  this  organism  in  very  large  numbers  in  a  case  where 
skatol  has  been  present,  whereas  flasks  prepared  with  the  same 
media  and  the  same  bacteria  plus  magnesium  carbonate  have 
failed  to  show  this  microorganism  and  have  also  failed  to  show 
skatol.     In  these  cases  the  difference  between  these  flasks  as  re- 
gards other  microorganisms  than  the  one  mentioned  have  been 
slight.     The  subject  is  difficult  of  investigation.     One  might  sup- 
pose that  the  faecal  bacteria  from  a  case  in  which  the  intestine 
contains  considerable  skatol  would  form  skatol  when  grown  in 
bouillon.     I  have  never  found  this  to  be  the  case.     Indol  is  formed, 
not  skatol. 

2  "  On  a  Relation  between  Skatol  and  the  Dimethylamidobenz- 
aldehyde Reaction  of  the  Urine,"  Journ.  BioL  Chem.,  i,  p.  251, 
1906. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      241 

In  most  cases  in  which  the  faeces  contain  considerable 
skatol  the  urine  gives  a  strong  reaction  with  dimethyl- 
amidobenzaldehy  de . 

Skatol  behaves  in  the  organism  much  like  indol  as 
respects  its  toxic  properties,  although  it  is  somewhat 
less  poisonous.  There  is  seldom  reason  to  attribute  to 
skatol  any  definite  pathological  effects,  as  it  is  formed  in 
quantities  too  small  to  fall  under  suspicion.  It  is  pos- 
sible, however,  that  like  phenol  it  may,  under  some  con- 
ditions, play  an  auxiliary  part  in  association  with  other 
substances  in  damaging  living  cells.1 

Indol.  —  It  has  long  been  known  that  indol  is  a 
product  of  putrefactive  decomposition  of  proteids,  and 
Baumann  showed  many  years  ago  that  this  substance  is 
formed  in  the  large  intestine  in  the  course  of  putrefac- 
tive processes  occurring  there.  He  showed,  moreover, 
that  the  absorption  of  indol  from  the  intestine  is  followed 
by  the  appearance  of  indican  in  the  urine.  Some  ob- 
servers have  concluded  that  the  indican  of  the  urine 
may  in  part  depend  on  the  liberation  of  indol  from  the 
breaking  down  of  body  cells.  I  regard  the  evidence  in 
favor  of  this  view  as  unsatisfactory  and  believe  that  the 
indican  of  the  urine  depends  exclusively  on  the  resorp- 
tion  of  indol  from  the  intestinal  tract  excepting  in  those 
cases  in  which  pathological  processes  such  as  a  putrid 
abscess  are  associated  with  the  formation  of  the  base. 

The  observation  has  been  repeatedly  made  by  clini- 

1  There  is  an  excellent  discussion  of  the  fate  of  skatol  to  be  found 
in  a  recent  paper  of  Porcher  and  Hervieux,  entitled  "Untersuch- 
ungen  uber  das  Skatol,"  Zdtschr.  f.  physiol.  Chem.,  xlv,  p.  487, 
1905. 

R 


242      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

cians  that  persons  in  whom  a  very  strong  indican  reac- 
tion can  be  obtained  in  the  urine  during  a  long  period 
of  time  invariably  suffer  from  nervous  or  dyspeptic  dis- 
orders, and  many  careful  physicians  have  believed  that 
there  is  some  causal  connection  between  the  absorption 
of  indol  from  the  intestine  and  the  development  of  func- 
tional nervous  or  nutritional  derangements.  I  believe 
that  in  recent  years  the  grounds  for  this  conviction  have 
been  considerably  strengthened.  Nevertheless,  it  can 
hardly  be  said  that  the  relation  between  the  absorption 
of  indol  and  the  symptoms  of  intoxication  in  man  has 
ever  been  placed  upon  a  firm  scientific  basis.  I  believe 
that  I  have  myself  underestimated  the  importance  of 
indol  as  a  toxic  agent  in  man,  and  desire  to  present  here 
evidence  which  has  lately  come  to  light  in  regard  to  the 
influence  of  indol  on  the  animal  organism.  For  this  rea- 
son I  shall  discuss  the  subject  of  indol  poisoning  some- 
what fully. 

Indol  is  not  a  product  of  the  tryptic  digestion  of  proteids, 
and  probably  cannot  be  formed  in  the  course  of  physio- 
logical processes  without  the  intervention  of  organized 
ferments  such  as  bacteria.  In  the  human  intestine  the 
presence  of  indol  is  dependent  on  the  action  of  living 
bacteria,  although  it  is  likely  that  the  action  of  the  diges- 
tive juices  may  prepare  the  way  for  the  attack  of  bacteria 
on  proteid  material.  The  indol  produced  in  the  intes- 
tine is,  like  skatol,  dependent  on  the  production  of  a 
more  complex  substance  known  as  tryptophan.  A  very 
careful  study  of  the  chemical  constitution  of  tryptophan 
was  lately  made  by  Gowland  Hopkins  of  Cambridge 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      243 

University.1  He  ascribed  to  it  the  constitution  of 
skatol-amido-acetic  acid,  but  it  has  been  shown  by  other 
workers  that  there  is  evidence  for  considering  trypto- 
phan  as  an  isomer  of  skatol-amido-acetic  acid;  namely, 
indol-amido-propionic  acid. 

It  has  been  known  since  the  days  of  Claude  Bernard 
that  tryptophan  arises  at  an  early  period  in  the  putre- 
faction of  proteids.  It  was  further  observed  that  while 
the  tryptophan  color  reaction  is  almost  always  observed 
in  the  early  stage  of  putrefaction,  it  later  disappears. 
The  cause  of  this  disappearance  is  the  further  cleaving 
action  of  bacteria  or  unorganized  ferments.  Hopkins 
was  able  to  show  that  the  action  of  bacteria  upon  trypto- 
phan may  lead  to  the  formation  of  indol,  skatol,  indol- 
acetic  acid,  and  indol-propionic  acid.  An  endeavor  was 
made  to  determine  the  influence  of  individual  types  of 
bacteria  upon  the  cleavage  of  tryptophan,  and  it  was 
found  that  B.  coli  is  capable  of  giving  rise  to  considerable 
yields  of  indol  at  the  same  time  that  it  produces  indol- 
acetic  acid.  Observations  with  cultures  of  symptomatic 
anthrax  representing  a  typical  spore-bearing  anaerobe, 
showed  that  this  organism  is  able  to  make  indol-propionic 
acid.  At  present,  however,  there  is  no  evidence  that 
more  than  a  small  proportion  of  tryptophan  in  a  medium 
is  converted  into  indol  through  the  action  of  putrefactive 
anaerobes.  I  studied  many  years  ago  the  influence 

1  Hopkins,  F.  Gowland,  and  Sydney  W.  Cole,  "Contributions 
to  the  Chemistry  of  Proteids,"  Ft.  II,  "The  Constitution  of  Tryp- 
tophane  and  the  Action  of  Bacteria  upon  It,"  Journ.  of  Physiol., 
xxix,  p.  451,  1903. 


244      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

of  introducing  large  numbers  of  B.  coli  communis, 
proteus  vulgaris  of  Hauser,  and  B.  acidolactici  into  the 
intestinal  tract  of  dogs,  with  a  view  to  determining  the 
effect  upon  indol  production.  It  was  found  that  the  in- 
jection of  pure  cultures  of  colon  bacilli  into  the  jeju- 
num of  dogs  was  followed  by  an  increase  in  the  indican 
reaction  of  the  urine  and  an  increase  in  the  output  of  the 
ethereal  sulphates.  In  order  to  exclude  the  introduction 
of  indol  into  the  intestine  in  the  course  of  these  experi- 
ments large  numbers  of  colon  bacilli  were  grown  on  agar- 
plates  and  washed  in  salt  solution.  The  introduction  of 
the  living  bacteria  was  followed  by  an  increase  in  the 
indican  of  the  urine,  whereas  the  introduction  of  sterile 
cultures  prepared  in  the  same  way  showed  at  most  only 
a  slight  increase  in  the  indican  excretion.  The  inference 
was  drawn  that  the  small  amount  of  indol  introduced  in 
feeding  experiments  made  with  colon  bacilli  does  not 
account  for  the  marked  increase  in  indican  which  was 
noted  in  these  experiments  and  that  this  increase  is  to 
be  attributed  to  the  action  of  the  colon  bacilli  themselves 
growing  upon  a  suitable  medium.  Similar  experiments 
were  made  with  pure  cultures  of  proteus  vulgaris  with  neg- 
ative or  slight  effects  as  regards  the  excretion  of  indican. 
The  lactic  acid  bacilli  employed  in  similar  experiments 
in  which  cultures  were  injected  directly  into  the  small 
intestine  showed  a  tendency  to  cause  a  reduction  in  the 
excretion  of  indican  and  of  the  ethereal  sulphates.1 

1  Herter,  "  On  Certain  Relations  between  Bacterial  Activity  in 
the  Intestine  and  the  Indican  of  the  Urine,"  Brit.  Med.  Jour., 
II.  p.,  1847,  1897. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      245 

There  are  many  persons  from  whose  intestines  it  is 
impossible  to  recover  indol  at  all  or  in  more  than  a  mere 
trace.  This  is  particularly  the  case  with  young  children 
and  young  adults.  There  are,  however,  some  older 
persons  who,  although  suffering  from  disorders  of  diges- 
tion, do  not  form  indol  in  the  digestive  tract.  On  the 
other  hand,  the  production  of  considerable  quantities  of 
indol  in  the  large  intestine  is  a  feature  of  many  instances 
of  intestinal  putrefaction,  and  in  some  cases  the  quantity 
formed  is  large.  One  may  find  as  much  as  fifty  to  sixty 
milligrams  of  indol  by  the  naphthaquinone  method  in 
one  hundred  grams  of  the  fresh  stool.  This  probably 
approaches  the  maximal  amount  present  at  any  one 
time.  It  is  of  course  clear  that  such  indol  production 
is  distinctly  pathological  in  occurrence.  Its  production 
in  smaller  amounts  permitting  the  recovery  of  five 
milligrams  in  one  hunndred  grams  of  moist  faces  is 
no  uncommon  occurrence,  and  such  indol  production 
may  or  may  not  be  associated  with  the  development 
of  intestinal  or  nervous  or  other  disturbances.  The 
significance  of  the  indol  produced  during  putrefaction  in 
the  intestine  depends  upon  its  absorption  into  the  organ- 
ism through  the  intestinal  wall.  That  this  occurs  in  con- 
siderable amounts  is  shown  by  the  appearance  of  large 
quantities  of  indican  in  the  urine  of  persons  in  whom 
the  intestine  contains  large  amounts  of  indol.  A  close 
relationship  between  the  quantity  of  indican  in  the  urine 
and  of  indol  formation  in  the  intestine  is  not  always 
demonstrable.  The  faeces  may  contain  little  indol  while 
the  urine  holds  much  indican.  Conversely,  the  fseces 


246      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

may  contain  a  considerable  quantity  of  indol;  and  owing 
to  imperfect  absorption  the  urine  may  contain  only 
moderate  quantities  of  indican.  Upon  the  whole,  how- 
ever, if  one  considers  the  findings  from  day  to  day  over 
a  considerable  period  of  time,  it  holds  true  that  there  is  a 
rough  relation  between  the  indol  formed  in  the  intestine 
and  the  quantity  of  indican  excreted.  In  conditions  of 
health  the  absorption  of  moderate  quantities  of  indol 
from  the  intestine  is  followed  by  the  rapid  oxidation  of 
indol  to  indoxyl  or  some  indoxyl  compound,  and  this 
oxidation  is  associated  with  or  followed  by  a  synthesis 
with  sulphuric  acid,  occurring  mainly  in  the  liver  and 
partly  in  the  muscles,  and  which  results  in  the  produc- 
tion of  the  indoxyl-potassium-sulphate  of  the  urine.  It  is 
the  indoxyl-potassium-sulphate  (or  indican)  of  the  urine 
which  on  further  oxidation  yields  indigo.  Something  is 
now  known  in  regard  to  the  fate  of  indol  in  the  organism. 
While  it  is  true  that  in  general  the  aromatic  compounds 
of  putrefaction  are  resistant  to  oxidation,  it  is  probable 
that  indol  when  introduced  in  moderate  quantities  into 
the  organisms  of  carnivora  and  omnivora  suffers  a 
break-down  both  in  the  pyrrol  ring  and  the  benzene 
ring.  That  is  to  say,  a  portion  of  the  indol  is  burned 
completely  in  the  organism.  This  view  is  based  partly 
on  what  has  been  found  to  be  the  case  for  phenols  and 
especially  for  cresol,1  and  partly  as  direct  observations 
on  the  facts  of  ingested  indol. 

1  Blumenthal,  "  Biochemische  Untersuchungen  iiber  Vergiftung 
und  Entgiftung  bei  der  Lysolvergiftung,"  Biochem.  Zeitschr.,  i, 
p.  135,  1906.  The  author  found  that  only  from  twenty  to 
twenty-five  per  cent,  of  the  cresol  introduced  into  the  animal 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      247 

It  was  shown  by  Herter  and  Wakeman  *  that  the  living 
cells  of  the  body,  especially  the  hepatic  and  renal  cells 
and  the  epithelial  cells  of  the  intestinal  tract,  have  the 
power  of  absorbing  considerable  quantities  of  indol  as 
well  as  of  phenol  and  of  tying  them  loosely  in  such  a  way 
that  these  bodies  cannot  be  recovered  by  distillation. 
Owing  to  this  property  of  the  cells,  by  which  they  hold 
these  aromatic  bodies  while  subjecting  them  to  oxidation 
and  pairing,  the  nervous  system  is  screened  from  their 
action.  The  importance  of  this  screening  action  is 
considerable,  for  the  presence  of  indol  or  phenol  in  very 
slight  concentration  in  the  blood  of  the  carotid  artery 
suffices  to  induce  violent  nervous  excitation  followed 
by  a  depression  of  nervous  function.  It  is  very  notice- 
able that  the  capacity  of  different  animals  to  remove 
indol  from  the  circulation  after  intravenous  injections 
differs  greatly  in  individuals  of  the  same  species.  What 
is  particularly  striking  is  the  fact  that  in  those  animals 
which  do  not  possess  livers  capable  of  promptly  removing 
the  greater  part  of  the  indol,  the  nervous  system  falls  a 
prey  to  the  action  of  the  poison.  Conversely,  it  is  also 
true  that  in  those  animals  in  which  nervous  symptoms  are 
very  pronounced  after  such  injections  of  indol,  it  is  found 
that  the  blood  and  brain  hold  considerable  indol,  whereas 
the  liver  may  be  shown  to  have  fallen  far  below  its  nor- 
mal capacity  in  the  removal  of  the  poison  from  the  blood. 

organism  could  be  found  again  in  the  urine  when  the  doses  are 
moderate  in  amount. 

1  Herter  and  Wakeman,  "The  Action  of  Hepatic,  Renal,  and 
Other  Cells  on  Phenol  and  Indol,"  Journ.  of  Exper.  Med.,  iv, 
p.  307,  1899. 


248      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

It  may  be  regarded  as  settled  that  the  liver,  muscles, 
intestinal  epithelium  (and  other  cells)  normally  exert  a 
protective  action  to  the  nervous  system  in  screening  it 
from  the  effects  of  an  injurious  percentage  of  indol  in 
the  blood  by  the  ability  of  these  structures  to  quickly 
bind  any  indol  which  comes  to  them.  It  may,  moreover, 
be  regarded  as  established  that  the  same  dose  of  indol 
administered  to  two  human  beings  of  about  equal 
weight  may  regularly  give  rise  to  more  pronounced  ner- 
vous manifestations  in  one  than  in  the  other.  While 
these  inequalities  may  be  due  partly  to  differences  in  the 
rapidity  of  absorption,  no  striking  differences  due  to  this 
factor  were  noticeable  in  the  excretion  of  indican  in  the 
urine,  and  it  appears  more  probable  that  the  differences 
in  the  observed  toxic  effects  were  dependent  on  inequali- 
ties in  different  persons  in  respect  to  their  ability  to 
oxidize  indol  and  to  pair  it  with  sulphuric  acid.  The 
probability  that  individual  differences  in  the  oxidizing 
capacity  of  the  tissues  of  different  persons  might  play  a 
part  in  determining  the  toxic  effects  of  indol  made  it 
desirable  to  get  experimental  evidence  as  to  the  in- 
fluence of  the  imperfect  oxidizing  action  of  the  cells  on 
the  fate  of  indol  in  the  body.  Such  experiments  have 
been  planned  and  made  by  Dr.  A.  N.  Richards  and  Dr. 
J.  Rowland,  and  their  results  are  of  such  interest  for  the 
general  pathology  of  intoxications  as  well  as  for  the 
question  of  indol  poisoning,  that  I  shall  speak  of  them  at 
some  length.1 

1  The  details  of  these  observations  have  not  yet  been  published, 
and  I  feel  under  obligations  to  Dr.  Richards  and  Dr.  Rowland  for 
permitting  me  to  use  their  notes. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      249 

To  reduce  the  oxidizing  processes  in  the  cells,  animals 
were  poisoned  with  hydrocyanic  acid,  a  substance  which 
possesses  a  high  degree  of  power  to  depress  the  ability 
of  animal  cells  to  take  up  oxygen  from  the  blood.  The 
effect  of  dyspnoea  from  tracheotomized  animals  was 
also  investigated  to  some  extent  and  similar  observa- 
tions were  made  upon  the  influence  of  chloroform  given 
to  the  point  of  narcosis  upon  the  fate  of  indol. 

In  general  it  may  be  said  that  rats,  mice,  guinea-pigs, 
and  dogs  subjected  to  subcutaneous  injections  of  potas- 
sium cyanide  too  small  in  themselves  to  cause  marked 
symptoms,  were  later  subjected  to  subcutaneous  or  peri- 
toneal injections  of  indol  or  phenol  in  watery  solution 
or  in  oil.  The  symptoms  observed  in  such  cases  were 
compared  with  those  obtained  from  the  injection  of 
indol  or  phenol  without  any  preceding  treatment  with 
potassium  cyanide.  The  result  almost  regularly  ob- 
served was  that  the  convulsive  twitching  which  is  char- 
acteristic of  the  action  of  the  phenol  and  of  indol  was  of 
greater  intensity  and  longer  duration  in  the  animals 
subjected  to  potassium  cyanide  than  in  the  case  of  the 
control  animals.  For  example,  into  a  guinea-pig  weigh- 
ing 370  gm.  was  injected  0.0003  gm.  of  indol  per  gram 
of  body  weight.  The  characteristic  twitching  came  on 
in  eight  minutes  and  lasted  ninety-seven  minutes.  It 
was  mild  in  character.  Into  another  guinea-pig,  weigh- 
ing 380  gm.,  0.005  mg.  of  potassium  cyanide  per  gram 
of  body  weight  was  injected  together  with  0.0003  gm. 
indol  per  gram  of  body  weight.  The  twitching  began 
in  two  minutes,  was  much  more  violent  than  in  the 


250      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

control  animal,  and  lasted  for  five  hours.  Experiments 
were  made  which  showed  that  the  lengthening  effect  is 
not  due  to  a  decreased  rate  of  absorption  dependent  on 
the  depression  of  the  circulation  by  potassium  cyanide. 
Experiments  were  also  made  to  determine  whether 
after  subcutaneous  injections  of  indol  any  uncombined 
indol  may  be  excreted  by  the  gastro-intestinal  tract,  and 
if  so,  under  what  conditions  such  excretion  occurs.  For 
example,  in  a  dog  weighing  eleven  kilos  the  small  intestine 
in  one  foot  of  its  extent  (in  the  region  just  above  the 
ileocsecal  valve)  was  severed  by  Dr.  Maury  from  the 
main  gut  and  the  ends  sewed  into  the  abdominal  wall. 
The  cut  ends  of  the  main  gut  were  joined  by  end-to-end 
anastomoses.  Complete  recovery  occurred  and  the 
health  of  the  dog  was  apparently  perfect.  The  mucous 
membrane  at  the  fistulous  openings  was  normal. 
One  month  later  an  experiment  was  made  in  which 
0.5  gm.  of  indol  dissolved  in  ten  cubic  centimeters  of  oil 
was  injected  subcutaneously.  No  symptoms  developed. 
The  loop  of  gut  was  washed  out  at  intervals  of  one-half 
hour  during  the  following  nine  hours,  and  no  indol  could 
be  detected  in  the  distillate  by  means  of  the  naphthaqui- 
none  reaction.  The  urine  obtained  by  catheter  forty-five 
minutes  after  injection  of  indol  gave  an  extremely  intense 
indican  reaction.  Repeated  examinations  showed  little 
falling  off  in  the  intensity  of  the  reaction  until  the  lapse 
of  twenty-two  hours.  After  twenty-eight  hours  the 
urine  showed  a  normal  indican  reaction.  After  an  in- 
terval of  two  days,  in  which  the  animal  was  apparently 
normal,  he  received  successive  injections  of  a  two  per 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      251 

cent,  solution  of  the  potassium  cyanide.  The  doses 
given  sufficed  to  cause  vomiting  and  some  muscular 
weakness,  but  no  convulsions.  The  injections  were 
given  during  a  period  of  two  and  one-half  hours.  At  the 
end  of  this  0.5  gm.  of  indol  was  injected  subcutaneously 
as  in  the  first  experiment.  No  further  vomiting  was 
noted,  but  twitching  of  the  muscles  of  the  face  and 
legs  was  more  marked  than  before.  One  and  one-half 
hours  after  the  indol  injections  the  animal  was  lively 
and  seemed  to  be  recovering.  Soon  after  he  received 
more  cyanide,  in  consequence  of  which  there  developed 
a  few  mild  convulsions.  There  was  much  prostration 
and  dyspnoea  and  some  fall  in  temperature.  The  odor 
of  indol  was  not  detected  at  the  fistulous  opening. 
Washings  made  from  the  gut  were  distilled  and  gave  a 
slight  reaction  for  indol.  It  was  found  that  the  indican 
reaction  in  the  urine  was  delayed  in  its  appearance  as 
compared  with  the  previous  experiment  and  that  the 
quantity  of  indican  as  judged  by  the  intensity  of  the 
color  was  considerably  less  developed  in  the  Obermeyer 
reaction.  The  quantity  of  indol  excreted  was  thus 
distinctly  less  than  during  the  previous  experiment.  The 
most  striking  feature  of  this  experiment  is  the  fact  that 
on  the  day  following  the  administration  of  indol  and 
potassium  cyanide  the  animal  remained  all  day  in  a 
condition  of  stupor  interrupted  by  periods  of  frantic 
and  poorly  coordinated  movements  in  which  he  recog- 
nized none  of  the  attendants  and  did  not  respond  to 
calls.  These  seizures  could  be  brought  about  by  local 
stimuli  and  resembled  the  behavior  seen  in  dogs  etherized 


252      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

or  chloroformed  during  the  period  of  lessening  conscious- 
ness which  precedes  that  of  complete  anaesthesia.  The 
animal  refused  food  and  water  and  showed  signs  of  in- 
creased peristalsis.  During  the  second  day  prostration 
and  stupor  were  less  marked,  but  uncoordinated  move- 
ments were  more  frequent  and  associated  with  a  state  of 
delirium  at  times  very  violent.  During  the  third  day 
the  condition  was  the  same.  During  the  fourth  day  the 
condition  was  the  same,  but  the  animal  was  weaker. 
Warm  diluted  milk  given  by  a  tube  was  instantly  vomited. 
On  the  sixth  day  egg- water  was  retained.  On  the 
seventh  day  death  occurred.  The  brain  was  found  to 
be  soft  and  congested.  The  cortical  nerve  cells  were 
found  to  be  oedematous  and  showed  excessive  chroma- 
tolysis.  The  mucous  membranes  of  the  loop  and  of  the 
duodenum  and  jejunum  were  considerably  congested. 
The  ileum  was  slightly  congested.  The  total  amount 
of  potassium  cyanide  given  to  this  animal  was  0.061  gm. 
in  six  doses  in  three  hours  during  the  first  period,  that 
is  before  giving  the  indol ;  after  the  indol,  that  is  in  the 
second  period,  0.085  gm.  was  given  in  four  doses  in  three- 
quarters  of  an  hour. 

The  leading  effects  of  the  poisoning  in  this  case  were, 
first,  a  prolongation  and  intensification  of  the  direct 
indol  effects  upon  the  nervous  system,  for  example,  the 
convulsive  twitching;  secondly,  a  delayed  transforma- 
tion of  indol  and  a  delayed  excretion  in  the  form  of 
indican;  third,  gastro-intestinal  symptoms;  fourth, 
blindness ;  and  lastly,  various  mental  symptoms.  Other 
similar  experiments  were  performed  which  clearly  showed 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      253 

that  when  indol  poisoning  is  preceded  by  the  adminis- 
tration of  physiological  quantities  of  potassium  cyanide 
the  indol  poisoning  takes  a  wholly  different  course  from 
that  observed  when  indol  alone  is  injected.  As  it  is 
known  that  potassium  cyanide  depresses  the  ability  of 
the  cells  to  take  up  oxygen,  it  is  reasonable  to  attribute 
to  this  depression  in  the  oxidizing  capacity  of  the  body 
cells  the  failure  of  the  organism  normally  to  oxidize  the 
injected  indol.  It  is  not  unreasonable  to  suppose  that  in 
chronic  disease  in  which  the  cells  most  concerned  in 
oxidation,  such  as  the  liver  cells,  have  been  structurally 
damaged,  that  the  ability  to  transform  indol  is  less  than 
in  a  state  of  health.  Such  alterations  are  common  in 
human  beings  as  a  result  of  infections,  alcoholism,  and 
intoxications,  etc.,  and  the  experiments  just  quoted 
enable  us  to  understand  how  under  such  pathological 
conditions  the  absorption  of  a  moderate  quantity  of 
indol  from  the  intestine  may  be  more  harmful  to  the 
central  nervous  system  than  is  the  case  in  persons  whose 
cells  have  suffered  little  deterioration  as  the  result  of 
disease. 

As  to  the  effects  of  absorbed  indol  upon  the  organism 
in  disease  it  is  necessary  to  speak  with  caution,  since  there 
is  no  evidence  that  indol  is  the  only  toxic  substance 
absorbed  in  those  cases  where  it  enters  the  organism 
from  the  gut.  Some  light  is  thrown  on  the  question  by 
experiments  made  through  administering  indol  to  normal 
men  by  the  mouth.  In  one  of  the  cases,  a  robust  young 
man  whose  urine  had  been  free  from  indican,  felt  no  effect 
from  large  doses  given  until  after  several  days'  adminis- 


254      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

tration,  when  the  influence  on  the  nervous  system  be- 
came distinct  and  led  to  irritability,  headache,  flight  of 
ideas,  etc.  It  should  be  noted  that  the  quantity  of  indol 
administered  in  this  case  was  probably  in  excess  of  any 
amount  that  would  be  absorbed  from  the  intestine,  even 
in  the  most  pronounced  pathological  condition.  It 
would  not,  however,  be  safe  to  infer  from  this  that  smaller 
doses  would  have  been  harmless ;  for  while  such  smaller 
doses  might  have  produced  little  or  no  effect  if  given 
during  a  few  days  to  a  normal  person,  it  is  not  unlikely 
that  its  long-continued  administration  would  have  led 
to  symptoms.  But  here  again  it  must  be  emphasized 
that  the  significance  of  indol  absorption  for  the  organism 
must  depend  largely  on  the  ability  of  the  organism  to 
quickly  oxidize  and  pair  the  indol  to  indoxyl-potas- 
sium-sulphate. 

The  idea  that  the  circulation  of  free  indol  in  the  blood 
may  act  in  a  depressing  manner  upon  muscular  struc- 
tures is  suggested  by  the  rapid  muscle  fatigue  which 
comes  on  in  some  persons  who  have  suffered  for  a  long 
period  of  time  from  a  high  grade  of  indicanuria.  It  is 
also  suggested  by  the  observations  which  I  have  made 
that  moderate  doses  of  indol  by  the  stomach  may  be 
followed  in  normal  persons  by  a  sense  of  muscle  fatigue, 
which  has  worn  off  rapidly  on  prolonged  exercise.  Pro- 
fessor Fred.  S.  Lee  of  Columbia  University  was  so  kind 
as  to  undertake  experiments  upon  the  muscles  of  cold- 
blooded animals  and  mammals  with  a  view  to  determining 
the  influence  of  indol  upon  the  onset  of  muscle  fatigue. 
His  results  are  expressed  in  the  f ollowing  notes :  — 


INFECTIONS  OF  THE  DIGESTIVE  TRACT     255 

"Experiments  have  been  performed  on  the  muscles  of  frogs 
and  cats.  The  method  has  been  to  irrigate  corresponding  muscles 
for  a  given  length  of  time  —  the  one  with  physiological-salt  solu- 
tion, the  other  with  physiological-salt  solution  plus  a  small  quan- 
tity of  the  drug,  and  then  to  stimulate  the  muscles  and  record  the 
contraction  and  the  amount  of  work  done  before  exhaustion  sets  in. 

"Indol  in  0.05  per  cent,  solution  —  that  is,  one  part  to  2000 

—  causes  an  early  fatigue  of  the  muscles  and  a  diminution  in  the 
amount  of  work  of  which  the  muscle  is  capable.     In  a  specific 
experiment  the    indolized  muscles  performed  24,320  g.  mm.  of 
work  before  it  became  exhausted,  while  at  the  same  time  the  cor- 
responding normal  muscle  performed  44,000  g.  mm.  of  work,  and 
was  still  capable  of  doing  more.     The  work  actually  accomplished 
by  the  two  muscles  was  100  (normal) :  55  (indol) . 

"Phenol  in  0.05  per  cent,  solution  —  that  is  one  part  to  2000 

—  usually  puts  the  muscle  into  a  better  working  condition  than 
that  of  the  normal  muscle.     In  a  specific  experiment  the  phenolized 
muscle    performed  7550  g.  mm.  of  work  before  it  became  ex- 
hausted, while  at  the  same  time  the  corresponding  normal  muscle 
performed  only  4400  g.  mm.  of  work.      The  work  actually  ac- 
complished by  the  two  muscles  was  100  (normal) :  171  (phenol). 
This  favorable  action  of  phenol  is  followed,  however,  by  the  re- 
verse effect,  the  phenolized  muscle  usually  becoming  exhausted 
before  the  normal  muscle.     In  0.1  per  cent,  solution  —  that  is, 
one  part  to  1000  —  the  effect  of  phenol  is  like  that  of  indol ;   in 
other  words,  the  phenolized  muscle  performs  less  work  and  be- 
comes fatigued  more  readily  than  the  normal  one." 

Still  more  important  than  the  foregoing  experiments 
is  the  following  observation  by  Dr.  Lee :  — 

"The  two  muscles  of  a  cat  were  irrigated  for  half  an  hour,  the 
one  with  whipped  blood,  the  other  with  whipped  blood  to  which 
indol  had  been  added  in  0.004  per  cent,  solution;  in  other  words, 
one  part  of  indol  to  25,000.  The  normal  muscle  then  performed 
34,400  g.  mm.  of  work,  while  the  indolized  muscle  performed  only 
12,880  g.  mm.  —  the  ratio  of  normal  work  to  indolized  work  is 
100:37." 

This  shows  that  indol  in  very  minute  quantity  acting 
for  a  long  time  on  the  muscle  diminishes  its  working 


256      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

power ;  an  observation  of  much  significance,  since  it 
gives  an  experimental  basis  to  the  suspicion  that  indol  is 
capable  of  acting  as  a  depressant  to  the  muscular 
mechanism.  The  most  pronounced  clinical  indications 
of  such  action  are  perhaps  those  derived  from  some 
cases  of  myasthenia  gravis.  Dr.  Tuttle  of  the  Pres- 
byterian Hospital  tells  me  that  he  has  lately  had  under 
observation  a  patient  whose  clinical  history  corresponds 
to  that  of  myasthenia  gravis  and  in  whom  the  only 
objective  sign  of  a  pathological  condition  was  an  intense 
and  persistent  indicanuria  which  was  not  much  modi- 
fied by  any  treatment  which  was  instituted.  It  is  clear 
that  cases  of  this  type  should  be  most  carefully  scruti- 
nized from  the  standpoint  of  the  possibility  that  the 
depression  of  muscle  function  is  dependent  on  the  action 
of  aromatic  products  upon  the  muscles.1 

The  rapid  onset  of  fatigue  observed  experimentally 
in  muscles  that  have  been  irrigated  with  indol  and  the 
curves  which  such  muscles  show  are  presumably  not 
specific  for  indol.  They  derive  their  significance  for  the 
human  subject  from  the  fact  that  indol  is  the  only 
aromatic  product  which  is  known  to  be  absorbed  in 
quantities  sufficient  to  render  it  probable  that  the  indol 
has  a  toxic  influence  upon  the  neuro-muscular  system. 
The  absorption  of  skatol  may  act  in  an  accessory  manner 
to  heighten  the  effect  induced  by  indol  poisoning,  but  the 

1 1  am  told  that  there  are  cases  of  myasthenia  gravis  in  which 
the  indican  of  the  urine  is  not  excessive.  This  fact  is  not  neces- 
sarily a  valid  argument  against  the  idea  that  indol  acts  as  a  muscle 
poison  in  myasthenia  gravis,  for  it  is  true  that  the  given  derange- 
ments of  function  may  arise  from  more  than  one  poison. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      257 

absorption  of  considerable  quantities  of  skatol  must, 
I  think,  be  an  exceptional  phenomenon  in  man.  In 
some  cases  of  excessive  intestinal  putrefaction  in  child- 
hood associated  with  a  retardation  in  growth  and  ab- 
dominal distension  there  is  clearly  a  poisoning  of  the 
muscular  system.  These  children  show  signs  of  fatigue 
very  rapidly  and  in  some  cases,  where  the  condition  has 
come  on  in  early  life,  they  are  slow  in  learning  to  walk. 
In  such  cases  there  is  not  only  a  large  amount  of  indican 
in  the  urine  but  a  considerable  excretion  of  phenol.  It  is 
quite  likely  that  the  phenol  in  these  cases  plays  a  part 
in  bringing  about  the  depression  of  muscular  action. 
Perhaps  in  some  instances  it  is  as  much  a  factor  in 
inducing  fatigue  as  is  indol.1 

INDICANURIA 

The  term  "  indicanuria"  is  used  to  designate  the  pres- 
ence of  an  abundance  of  indican  in  the  urine  as  demon- 
strated by  the  presence  of  strong  reactions  (with  the  form- 
ation of  indigo)  on  the  use  of  Obermeyer's  test  or  similar 
tests.  It  has  already  been  mentioned  that  in  normal  child- 
hood little  or  no  indican  appears  in  the  urine.  There  are 
also  many  adults  who  seldom  show  the  presence  of  indican 
in  the  urine.  There  are  also  many  adults  who  show  a 

1  The  primary  beneficial  effect  of  phenol  on  muscle  action 
observed  by  Dr.  Lee  does  not  speak  against  this  view,  as  this 
effect  is  one  that  soon  gives  way  to  fatigue. 

The  very  interesting  observation  has  been  made  by  Dr.  Lee 
that  a  temporary  beneficial  action  is  exerted  on  muscle  by  all  the 
common  fatigue  products  studied  by  him. 


258       INFECTIONS  OF  THE  DIGESTIVE  TRACT 

moderately  strong  reaction  for  indican  in  the  urine 
during  a  long  period  of  time  (that  is,  most  of  the  time 
during  many  years)  and  still  retain  good  health  and  do 
not  suffer  obtrusively  from  digestive  disorders.  This 
is  true  of  many  students  who  live  sedentary  lives.  On 
the  other  hand,  there  are  persons  with  digestive  disorders 
who  show  little  or  no  indican  in  the  urine.  Finally, 
there  are  not  very  rare  instances  in  which  during  a  short 
or  a  considerable  period  the  urine  contains  very  large 
quantities  of  indican  so  that  the  reaction  with  Ober- 
meyer's  reagent  is  intense.  I  think  it  safe  to  say  that 
such  persons  are  seldom  free  from  clinical  evidences  of 
intestinal  disorder  and  that  often  there  are  also  in  these 
cases  some  indications  of  intoxication. 

Almost  every  physician  who  has  observed  considerable 
numbers  of  patients  with  reference  to  the  presence  or 
absence  of  indican  in  the  urine,  has  been  puzzled  to 
interpret  his  results.  For  he  has  no  sooner  begun  to 
attach  importance  to  the  presence  of  a  strong  indican 
reaction  in  certain  cases  than  his  faith  in  this  as  a  sign  of 
disease  has  been  shaken  by  the  fact  that  he  has  found  a 
strong  indican  reaction  in  the  urine  of  some  person  who 
is  apparently  well.  I  think  it  would  greatly  aid  us  in  the 
interpretation  of  the  meaning  of  indicanuria  if  we  took 
into  consideration  the  important  factor  of  the  ability 
of  the  organism  to  defend  itself  against  the  toxic  action 
of  indol  by  quickly  disposing  of  it.  It  is  of  course 
difficult  to  fashion  standards  for  the  judgment  of  this 
factor  of  defense.  But  there  are  certain  obvious  con- 
siderations which  bear  on  the  judgment  of  the  defensive 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      259 

powers  of  the  organism  for  oxidizing  and  pairing  indol. 
It  is  certain  that  the  oxidizing  powers  of  the  cells  in 
early  life  are  greater  than  in  later  life  and  that  on  this 
account  organisms  are  likely  to  suffer  more  from  the 
absorption  of  equal  amounts  of  indol  between  the  fiftieth 
and  seventieth  years  of  life  than  between  the  fifteenth 
and  thirtieth.  This  is  doubtless  true  quite  aside  from  the 
degenerations  that  occur  in  organs  which  have  been  sub- 
jected to  the  action  of  disease.  In  cases  where  the  ele- 
ment of  disease  has  entered  to  injure  the  liver,  kidney, 
intestinal  epithelium,  muscles,  and  other  structures, 
the  organism  naturally  becomes  more  sensitive  to  the 
action  of  indol  than  before  its  powers  of  oxidization  and 
synthesis  have  become  impaired.  There  are  very  many 
conditions  in  which  the  liver  undergoes  cirrhotic  or 
fatty  changes  or  in  which  both  of  these  processes  are 
marked  or  in  which  there  are  well-defined  parenchyma- 
tous  changes.  It  is  certain  that  such  persons  will  be 
especially  sensitive  to  the  action  of  all  kinds  of  poisons, 
including  that  of  indol.  We  have  therefore  in  judging 
of  the  significance  of  any  case  of  pronounced  indican- 
uria  to  consider  whether  it  occurs  in  a  young  person  or  in 
an  older  one ;  in  a  healthy  individual  or  in  one  whose  cells 
have  been  damaged  by  disease.  In  youth  it  is  com- 
paratively easy  to  find  a  diet  and  mode  of  living  under 
which  the  indican  can  be  made  to  disappear  largely  from 
the  urine.  In  aged  persons  the  task  is  usually  more 
difficult,  especially  if  the  indicanuria  has  been  of  long 
duration. 
Aside  from  cases  of  indol  absorption  from  the  presence 


260      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

of  a  dead  foetus  or  an  abscess,  I  believe  that  indicanuria 
always  points  to  absorption  of  indol  from  the  intestinal 
tract.  There  is  no  convincing  evidence  that  the  autoly- 
sis  of  organs  during  life  yields  indol,  and  I  think  that 
such  a  source  may  be  regarded  as  a  negligible  factor  in 
dealing  with  cases  of  indicanuria.  Admitting,  however, 
that  indicanuria  is  of  intestinal  origin,  it  remains  to  be 
explained  why  it  is  present  in  some  cases  of  intestinal 
disturbance  and  not  in  others.  A  wholly  satisfactory 
answer  to  this  question  is  not  at  the  present  time  possible. 
Some  facts  which  bear  on  the  problem  maybe  stated  here. 
It  has  been  claimed  by  Pizenti  and  others  that  the  pres- 
ence of  pancreatic  juice  is  essential  to  the  production  of 
indicanuria.  This  claim  is  based  on  the  fact  that  indol  is 
a  product  of  proteolytic  cleavage.  The  proteid  food  en- 
tering the  intestine  is  supposed  to  be  attacked  vigorously 
by  the  abundant  tryptic  ferment  of  the  pancreatic 
juice,  and  this  decomposition  is  presumed  to  reach  so 
advanced  a  stage  as  to  lead  to  the  indol  production  from 
which  the  indicanuria  arises.  While  it  is  true  that 
indol  is  a  product  of  proteid  cleavage,  I  think  it  ex- 
tremely doubtful  whether  there  is  an  opportunity  for  the 
process  of  cleavage  to  go  so  far  as  to  yield  indol,  unless 
the  quantity  of  proteid  food  is  largely  excessive  and  thus 
delays  absorption.  Ordinarily  absorption  occurs  in  the 
peptone  and  amino-acid  stage  of  proteolytic  digestion. 
It  is  not  conceivable  that  in  the  absence  of  putrefactive 
bacteria  from  the  small  intestine  a  rapidly  proteolyzed 
meal  should  lead  to  the  formation  of  indol  in  the  intestine, 
since  indol  does  not  arise  from  tryptic  digestion.  It  has 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      261 

been  held  that  persons  with  pancreatic  disease  who  are 
unable  to  secrete  pancreatic  ferments  into  the  intestine 
do  not  develop  indicanuria.  This  is  surely  a  mistaken 
view.  I  have  observed  indican  reactions  to  persist  in 
dogs  from  which  the  pancreas  had  been  removed,  and  I 
have  met  with  some  of  the  most  marked  instances  of 
indicanuria  in  persons  in  whom  autopsy  or  operation 
showed  both  the  pancreatic  and  the  biliary  duct  to  be 
occluded. 

Intestinal  indicanuria  must  be  regarded  as  an  evidence 
of  intestinal  putrefaction.  It  is  commonly  easy  to  pro- 
duce it  experimentally  in  dogs  by  feeding  a  greatly 
excessive  quantity  of  meat.  Not  only  may  an  habitual 
indicanuria,  such  as  is  common  among  dogs,  be  increased 
by  excessive  feeding  of  meat,  but  the  condition  may  be 
induced  by  excessive  feeding  in  cases  where  the  urine 
was  previously  quite  free  from  indican.  The  explanation 
of  this  fact  appears  to  me  to  depend  on  the  presence  of 
putrefactive  bacteria  in  the  ileum  and  large  intestine  of 
the  dog.  If  we  examine  any  portion  of  the  large  intestine 
or  the  lower  ileum,  we  shall  usually  find  there  moderate 
or  considerable  numbers  of  anaerobic,  spore-forming, 
butyric-acid-producing  bacteria  as  well  as  colon  bacilli. 
These  anaerobes  have  the  power  of  attacking  native 
proteids  which,  under  suitable  conditions,  they  may 
energetically  hydrolyze.  Some  anaerobes  such  as  B. 
aerogenes  capsulatus  are  usually  unable  to  carry  the  de- 
composition as  far  as  indol  production.  The  colon  bacilli 
normally  present  in  the  intestine,  however,  are  able  to 
make  indol  from  peptones.  It  is  only  necessary,  there- 


262      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

fore,  to  feed  the  animal  so  excessive  a  quantity  of  meat 
that  small  masses  of  muscle  fiber  enter  the  lower  ileum 
or  the  large  intestine.  Here  they  will  be  attacked  by 
anaerobes  and  colon  bacilli  with  a  production  of  indol  and 
subsequent  development  of  indicanuria.  Naturally  any 
condition  favoring  stagnation  in  the  small  or  large 
intestine  will  help  to  bring  about  this  condition.  It  is 
possible  that  moderate  quantities  of  hydrolyzed  proteid 
reach  the  lower  part  of  the  ileum  owing  to  impaired 
absorption.  In  this  region  both  in  man  and  in  dogs  the 
colon  bacilli  are  numerous.  Under  these  circumstances 
it  is  not  necessary  for  anaerobes  to  take  part  in  the  attack 
on  the  already  hydrolyzed  proteid,  since,  as  repeatedly 
stated,  the  colon  bacillus  itself  suffices  to  do  this.  The 
effect  of  introducing  partially  hydrolyzed  proteids  into 
the  large  intestine  was  very  plainly  shown  in  the  following 
experiment.  A  healthy  dog  which  had  been  fed  on  meat 
in  moderate  quantities  gave  only  a  slight  reaction  for 
indican.  Fifty  cubic  centimeters  of  a  concentrated  egg 
and  meat  mixture  were  subjected  to  short  partial  tryptic 
digestion  (without  the  development  of  indol).  This 
material  was  sterilized  in  the  autoclave  and  then  injected 
into  the  transverse  and  ascending  colon  and  confined 
there  by  ligature.  Two  hours  later  the  indican  reaction  in 
the  urine  was  markedly  increased  and  at  the  end  of  ten 
hours  had  become  intense,  this  change  doubtless  having 
been  due  to  the  bacterial  attack  to  which  the  material 
was  subjected  in  the  large  intestine. 

There  are  some  persons  in  whom  the  imperfect  action 
of  a  cathartic  leads  to  the  development  of  headache, 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      263 

flatulence,  and  an  increase  of  the  indican  in  the  urine. 
The  explanation  of  this  is  to  be  sought  in  the  fact  that 
the  cathartic  causes  the  passage  of  native  proteids  and 
possibly  of  peptones  from  the  small  into  the  large  intes- 
tine, where  it  is  possible  to  attack  the  former  if  anaerobes 
be  present.  Presumably  in  persons  harboring  few  an- 
aerobic bacteria  this  effect  would  be  slight,  but  in  per- 
sons in  whom  organisms  of  the  class  of  B.  putrificus  or 
B.  aerogenes  capsulatus  are  abundant  one  would  expect 
the  appearance  of  considerable  indican  in  the  urine. 

The  influence  of  constipation  upon  the  development  of 
indicanuria  is  very  different  in  different  persons.  Most 
children  and  many  adults  may  go  without  a  movement 
for  several  days  and  still  fail  to  develop  indicanuria  if 
this  has  previously  been  absent.  There  are  other  per- 
sons in  whom  constipation  is  followed  by  a  marked 
increase  in  the  output  of  indican.  A  wholly  satisfactory 
explanation  of  this  difference  in  the  influence  of  constipa- 
tion upon  indol  formation  in  the  intestine  is  not  at  pres- 
ent possible.  Sufficient  bacteriological  data  are  lacking. 
A  probable  explanation  is  the  following.  The  formation 
of  indol  in  the  intestinal  tract  depends  on  the  decomposi- 
tion of  proteids  through  the  activity  of  microorganisms. 
If  the  colon  bacilli  have  for  any  reason  ascended  in  large 
numbers  above  their  usual  upper  limit,  namely  the 
ileum,  into  the  jejunum  or  duodenum,  they  will  act 
there  upon  peptones  formed  in  the  course  of  the  normal 
digestion  of  proteids.  From  such  peptones  they  will 
make  indol.  Under  these  circumstances  the  aid  of  putre- 
factive anaerobes  is  not  necessary  for  the  production  of 


264      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

indol.  If,  however,  there  is  no  ascent  of  the  colon  bacilli 
to  the  region  in  which  these  organisms  would  find  pep- 
tones to  attack,  the  abnormal  production  of  indol  is  not 
excluded,  for,  as  already  stated,  the  action  of  the  anaerobes 
in  the  ileum  and  large  intestine  permits  the  hydrolyzing 
of  proteids  which  then  fall  subject  to  the  colon  bacilli 
with  a  resulting  production  of  indol.  Both  these  methods 
of  indol  production  may  occur  in  the  same  individual, 
namely  its  production  in  the  small  intestine  through  the 
action  of  colon  bacilli  on  peptones,  and,  secondly,  the 
formation  of  indol  in  the  ileum  and  large  intestine  through 
the  combined  action  of  putrefactive  anaerobes  and  colon 
bacilli  acting  upon  such  native  proteids  as  may  have 
escaped  digestion  at  higher  levels.  The  occurrence  of 
constipation  may  be  considered  as  favoring  both  these 
methods  of  indol  production,  but  only  under  abnormal 
conditions  of  digestion.  The  stagnation  of  food  rem- 
nants and  bacteria  in  the  large  intestine  would  cause  no 
indol  production  according  to  the  hypothesis  here  set 
forth  unless  masses  of  undigested  proteid  or  hydrolyzed 
proteid  material  had  entered  the  region  of  the  large 
intestine.  The  stagnation  of  food  in  the  small  intestine 
would  not  lead  to  the  production  of  indol  there  except  in 
the  presence  of  colon  bacilli  or  other  microorganisms 
capable  of  making  indol  from  peptones  or  albumoses. 
Of  the  actual  ascent  of  such  bacteria  from  the  upper  level 
of  their  normal  habitat  into  the  higher  levels  of  the  small 
intestine  we  know  as  yet  very  little  that  is  definite. 
The  invasion  of  the  gall-bladder  by  colon  bacilli  under 
conditions  which  make  it  improbable  that  there  has  been 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      265 

any  passage  of  colon  bacilli  from  the  intestine  into  the 
blood  (and  thus  through  the  liver  into  the  gall-bladder) 
makes  it  likely  that  there  is  in  these  cases  an  ascent  of 
the  colon  bacilli  to  the  level  of  the  common  bile  duct. 
The  colon  bacilli  travel  so  rapidly  after  death  that  it 
is  only  through  very  early  autopsies  that  one  could  ob- 
tain evidence  of  the  presence  of  these  organisms  at  high 
levels  of  the  intestinal  tract.  Reliable  data  relating  to 
this  point  are  at  present  lacking.  There  is,  however, 
a  probability  that  in  altered  states  of  secretion  in  the 
small  intestine  incidental  to  subacute  or  chronic  enteritis 
the  colon  bacilli  do  ascend  above  the  level  of  their  normal 
habitat  and  thus  become  factors  in  the  production  of 
indol  and  hence  of  indicanuria. 

That  the  conditions  which  lead  to  pathological  indi- 
canuria are  not  always  the  same  is  rendered  probable 
by  the  marked  differences  in  the  amenability  of  this 
condition  to  treatment  which  have  been  observed  by  all 
clinicians  who  have  attempted  to  modify  this  condition 
in  a  variety  of  patients.  There  are  instances  in  which 
a  reduction  in  proteid  diet  is  in  itself  sufficient  to  greatly 
diminish  the  quantity  of  indican  excreted.  Reduction 
in  the  quantity  of  meat  which  is  daily  taken  by  a  patient 
is  often  efficacious  in  effecting  this  end.  The  explanation 
of  the  improvement  following  a  diminished  use  of  meat 
perhaps  lies  in  the  fact  that  on  the  more  limited  diet 
smaller  quantities  of  undigested  meat  pass  into  the  region 
of  the  associated  anaerobes  and  colon  bacilli.  A  change 
from  a  diet  containing  much  meat  to  one  in  which  milk 
is  substituted  for  meat  sometimes  leads  to  a  prompt 


266      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

reduction  in  the  output  of  indican.  The  improvement 
is  probably  due  to  the  more  ready  digestion  and  absorp- 
tion of  the  milk.  But  there  are  instances  in  which  the 
substitution  of  milk  for  meat  does  not  materially  influence 
the  output  of  indican  as  judged  by  the  Obermeyer 
reaction.  The  invasion  of  the  small  intestine  by  colon 
bacilli  (and  perhaps  putrefactive  anaerobes)  would 
satisfactorily  explain  this  phenomenon,  since  in  such  a 
case  even  the  more  rapid  absorption  incidental  to  a 
milk  as  compared  with  a  meat  diet  would  not  suffice  to 
elude  the  action  of  the  colon  bacilli  upon  peptones  formed 
in  the  course  of  digestion.  There  are  also  cases  in  which 
no  dietetic  measures  have  a  marked  influence  in  reducing 
the  excretion  of  indican.  That  is  to  say,  the  indicanuria 
remains  well  marked  whether  proteid  food  be  employed 
in  the  form  of  meat  or  milk  or  eggs  or  cereals.  Dr.  George 
A.  Tuttle  of  the  Presbyterian  Hospital  has  made  the 
observation  that  there  are  cases  of  indicanuria  which 
though  persisting  on  a  milk  diet  are  susceptible  of 
striking  improvement  or  complete  disappearance  through 
the  agency  of  potassium  iodide.  The  cases  of  this  type 
have  always  been  cases  of  marked  arterial  sclerosis 
and  some  of  them  have  had  a  history  of  syphilitic 
infection.  The  explanation  of  this  noteworthy  fact 
is  obscure.  The  possibility  occurs  to  one  that  the 
potassium  iodide  influences  favorably  the  circulation  in 
the  intestine  and  this  aids  rapid  absorption,  but  it  is 
also  possible  that  the  iodide  may  hi  some  way  increase 
the  oxidizing  activity  of  the  cells  mainly  concerned  with 
the  composition  of  indol  in  the  body,  notably  the 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      267 

liver  cells.1  The  increased  oxidation  of  indol  would 
lead  to  a  diminished  excretion  of  indican  and  perhaps 
to  its  complete  disappearance.  Dr.  Tuttle  tells  me  also 
that  he  has  had  patients  in  whom  the  administration  of 
iron  in  the  form  of  Basham's  mixture  has  soon  been 
followed  by  a  marked  lessening  of  the  indicanuria.  As 
this  has  occurred  in  cases  where  the  diet  has  been  care- 
fully studied  and  dietetic  measures  have  failed  to  give 
the  desired  relief,  Dr.  Tuttle  has  attributed  the  thera- 
peutic action  to  the  iron. 

It  is  worth  noting  that  wherever  there  is  a  persistent 
indicanuria  which  has  not  yielded  to  a  change  in  the 
character  of  the  proteid  food  nor  to  a  diminution  of  it 
nor  to  a  restriction  of  the  carbohydrates,  one  may 
rationally  employ  gelatin  as  a  nitrogenous  substance 
capable  of  replacing  in  some  degree  the  proteids  of  the 
diet.  Gelatin  does  not  contain  a  tryptophan  nucleus 
and  hence  cannot  yield  indol.  It  has  been  shown  by 
physiologists  that  the  metabolic  needs  of  the  organism 
for  nitrogen  may  be  in  part  met  by  the  use  of  gelatin, 
although  as  is  well  known  gelatin  alone  is  incapable 
of  maintaining  the  protoplasm  of  cells  where  proteids 
are  wholly  withdrawn  from  the  dietary.  I  consider  it 
entirely  safe  to  replace  a  portion  of  the  nitrogen  of  the 
food  by  gelatin  (in  the  form  of  jellies)  and  believe  I 
have  observed  a  falling  off  in  the  indican  of  the  urine  in 
consequence  of  this  substitution.  Clinically,  experience 

1  The  presence  of  iodides  in  a  urine  containing  indican  inter- 
feres with  the  Obermeyer  reaction,  but  this  source  of  error  appears 
to  have  been  eliminated  in  the  procedure  followed  by  Dr.  Tuttle. 


268      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

shows  plainly  that  in  the  treatment  of  indicanuria  one 
has  to  consider  not  only  the  proteid  food  which  is  given, 
but  also  the  carbohydrates.  With  many  persons  the 
excessive  use  of  carbohydrates  is  habitual  and  the  sub- 
stitution of  small  quantities  of  quickly  digested  carbo- 
hydrates like  rice  for  large  quantities  of  bread  or  sugars 
may  make  a  considerable  difference  in  the  amount  of 
indican  excreted.  Diastatic  enzymes  can  be  made  to 
render  good  service  in  this  connection.  Assuming  that 
the  persistent  indicanuria  in  the  cases  in  question  is  due 
at  least  in  part  to  the  upward  extension  of  colon  bacilli 
and  certain  putrefactive  anaerobes  into  the  small 
intestine,  it  seems  reasonable  to  believe  that  the  with- 
drawal of  excessive  carbohydrates  is  equivalent  to  a 
diminution  in  the  pabulum  on  which  the  microorganisms 
multiply  so  readily  with  the  production  pf  gas  and  acid 
and  indol. 

As  will  be  seen  in  speaking  of  the  treatment  of  chronic 
excessive  intestinal  putrefaction,  the  use  of  cathartic 
medication  is  usually  followed  very  promptly  by  a 
diminished  absorption  of  indol  from  the  intestine. 
Persons  suffering  from  great  indicanuria  are  apt  to  show 
a  marked  diminution  in  the  excretion  of  indican  after  the 
administration  of  calomel  or  cascara  or  a  saline  or  other 
cathartic.  The  indican  may  in  rare  instances  entirely 
disappear  temporarily.  This  effect  is,  however,  only 
of  very  short  duration.  The  diminished  excretion  of 
indican  is  due  of  course  to  the  mechanical  removal  of 
indol-forming  and  indol-containing  contents  of  the 
intestine.  A  diminished  absorption  of  indol  is  associated 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      269 

frequently  with  the  relief  of  certain  symptoms,  such  as 
headache  and  dizziness.  It  is  not  clear  that  these 
symptoms  are  due  wholly  to  the  excessive  indol  absorp- 
tion. Unfortunately  the  relief  is  temporary  and  is 
followed  by  a  continuance  of  the  original  putrefactive 
conditions  and  the  resumption  of  indicanuria.  Indeed, 
in  some  persons  constipation  following  catharsis  is 
associated  with  a  still  greater  excess  of  indican  in  the 
urine  than  has  been  habitual.  The  repeated  use  of 
cathartics  daily  or  at  somewhat  longer  intervals  for  the 
purpose  of  diminishing  the  absorption  of  toxic  sub- 
stances is  inadvisable,  for  it  ultimately  leads  to  a  loss 
in  weight  and  strength.  It  seems  unnecessary  to 
further  discuss  here  the  subject  of  indicanuria,  which 
is,  as  a  rule,  linked  with  other  intestinal  conditions 
requiring  consideration  and  which  therefore  it  is  not 
usually  advisable  to  single  out  as  the  sole  object  of 
treatment. 

THE    POSSIBILITY  OP   THE    OCCURRENCE    OF    INDOLEMIA 
AND   INDOLURIA 

It  naturally  occurs  to  any  one  who  considers  the 
phenomenon  of  indicanuria  and  the  conditions  leading 
to  it  that  in  extreme  instances  of  this  phenomenon, 
where  relatively  large  quantities  of  indol  have  to  be 
oxidized,  and  paired,  these  preparatory  processes  may 
sometimes  be  insufficiently  active  to  prevent  the  cir- 
culation of  indol  in  the  blood  in  such  concentration  as 
would  lead  to  the  appearance  of  free  indol  in  the  urine. 


270      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

The  occurrence  of  free  indol  in  the  urine  is  certainly 
a  very  exceptional  phenomenon  even  hi  cases  of  ex- 
perimental poisoning  with  indol.  In  the  combined 
cyanide  and  indol  experiments  of  Richards  and  How- 
land  it  was  found  that  a  trace  of  indol  sometimes  appeared 
in  the  urine.  It  is,  however,  noteworthy  that  in  the 
experiments  in  which  examinations  were  made  for  the 
detection  of  free  indol  in  a  loop  of  intestine  (after  poison- 
ing with  considerable  quantities  of  indol)  much  more 
indol  was  found  to  be  excreted  by  the  intestinal  loop 
than  was  excreted  into  the  urine.  This  fact  points 
decisively  to  a  relatively  difficult  excretion  of  indol  by 
the  kidney.  The  tests  employed  for  the  identification 
of  the  indol  included  Ehrlich's  dimethylamidobenzalde- 
hyde  and  the  /3-napthaquinone-sodium-monosulphonate 
reactions.  The  latter  reaction,  as  already  explained, 
is  absolutely  distinctive  for  indol. 

Although  it  is  thus  apparent  that  the  conditions  re- 
quired to  bring  about  the  excretion  of  free  indol  in  the 
urine  must  be  such  as  seldom  occur  spontaneously  in 
human  beings,  it  cannot  be  denied  that  traces  of  indol 
may  sometimes  appear  in  the  urine  in  the  course  of  ex- 
treme indicanuria.  In  a  few  instances  distillates  from  the 
urine  contained  a  body  which  strongly  suggested  indol. 
But  the  actual  proof  of  the  occurrence  of  free  indol  in  the 
urine  in  these  cases  of  extreme  indicanuria. does  not,  I 
think,  exist  at  present.  It  seems  probable  that  a  con- 
siderable concentration  of  indol  in  the  blood  is  nec- 
essary to  bring  about  the  phenomenon  of  indoluria,  and 
such  a  concentration  as  will  insure  this  leakage  into  the 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      271 

urine  must  be  of  very  exceptional  occurrence  under 
clinical  conditions.  This  fact  does  not  seem  to  me  to 
weaken  the  probability  that  it  is  not  very  uncommon 
for  the  blood  to  contain  traces  of  indol  in  some  cases 
of  extreme  intestinal  putrefaction.  The  proof  of  the 
presence  of  indol  in  the  blood  in  experimental  poisoning 
cases  is  easily  obtained,  but  I  know  of  no  instances  of 
extreme  indicanuria  in  which  any  attempt  has  been 
made  to  obtain  free  indol  from  the  blood.  The  demon- 
stration of  the  occurrence  of  indol  in  the  blood  even  in 
the  minutest  trace  would  be  of  especial  interest  in  those 
cases  of  indicanuria  in  which  nervous  symptoms  are 
extremely  pronounced. 

In  a  recent  paper  dealing  with  the  subject  of  indigouria, 
Porchet  and  Hervieux  have  reached  the  conclusion  that 
indol  is  in  itself  devoid  of  toxic  properties,  but  that 
indoxyl,  its  oxidation  product,  is  a  comparatively  poison- 
ous agent.  They  prepared  their  indoxyl  from  indoxyl 
carbonic  acid  and  injected  it  into  rabbits  but  fail  to 
give  the  doses  in  which  they  found  the  indoxyl  fatal. 
It  does  not  appear  to  me  that  the  opportunity  for  the 
occurrence  of  free  indoxyl  in  the  blood  or  tissues  can 
ever  be  good,  since  the  process  of  pairing  with  sulphuric 
acid  is  so  intimately  connected  with  the  oxidation  of  indol 
to  indoxyl  that  it  is  difficult  to  believe  any  significant 
amount  of  free  indoxyl  can  ever  be  present  at  one  time. 
One  may,  however,  admit  the  possibility  that  in  con- 
ditions of  extremely  abundant  absorption  of  indol  from 
the  intestine  there  might  be  formed  an  amount  of  indoxyl 
larger  than  usual,  within  a  time  insufficient  to  secure 


272       INFECTIONS  OF  THE  DIGESTIVE  TRACT 

its  complete  pairing.  Under  such  .conditions  it  might 
conceivably  be  a  factor  in  the  production  of  symptoms. 
As  compared,  however,  with  the  quantity  of  indol 
existing  as  such  in  the  organism,  it  seems  to  me  that  the 
indoxyl  must  be  insignificant.  Evidence  has  already 
been  offered  to  show  that  while  indol  is  not  a  highly 
toxic  substance  for  normal  carnivorous  or  omnivorous  ani- 
mals, it  becomes  much  more  toxic  when  conditions  arise 
under  which  there  is  defective  oxidation.  This  aspect  of 
the  question  of  the  toxicity  of  indol  is  one  which  has  not 
been  touched  upon  by  any  writers  upon  this  subject. 

Indigouria.  —  It  has  long  been  known  that  there 
occasionally  occur  cases  of  extreme  indicanuria  in  which 
the  urine  upon  standing  in  contact  with  the  air  gradually 
becomes  blue  and  may  liberate  a  pelicle  of  indigo  upon 
the  surface  of  the  urine  at  the  same  time  that  a  precipi- 
tate of  fine  particles  of  indigo  occurs  in  the  urine.  Such 
cases  are,  I  believe,  very  exceptional  and  do  not  arise 
except  where  the  indicanuria  has  been  of  long  standing. 
The  subjects  of  this  indigouria  are  almost  invariably 
badly  nourished  and  in  poor,  often  precarious,  health. 

Procher  and  Hervieux  1  have  lately  studied  experi- 
mental indigouria,  which  they  found  to  arise  when  larger 
quantities  than  one  or  two  grams  of  indol  are  administered 
by  the  stomach  to  dogs.  The  phenomena  as  they  appear 
in  the  urine  of  these  experimental  cases  are  essentially 
the  same  as  those  observed  in  man.  In  the  majority 

1  "  Recherches  experimentales  sur  les  chromogfenes  urinaires 
du  Groupe  de  ITndol'  (5*  M6moire)  "De  ITndigourie,"  Journ.  de 
Physiol.  et  de  Path,  gen.,  viii,  p.  841,  1906. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      273 

of  cases  the  pigment  which  is  separated  from  the  urine 
is  blue  in  color.  In  the  case  of  rabbits  the  substance 
separated  from  the  urine  is  red  in  color  and  represents 
the  presence  of  indirubin,  a  substance  closely  related  to 
indigo.  It  often  happens  in  indigouria  that  both  these 
substances  are  present  together.  The  onset  of  the  indigo- 
uria in  dogs  has  been  observed  after  three  or  four  hours 
from  the  time  of  the  administration  of  the  indol,  but  the 
phenomenon  is  at  its  height  after  six  or  eight  hours  have 
gone  by. 

Porcher  and  Hervieux  claim  to  have  detected  the 
presence  of  indoxyl  in  the  urine  of  dogs  which  had  been 
given  experimental  indigouria.  It  is  thought  by  them 
that  the  indoxyl-potassium-sulphate  (which  they  call 
the  indigouria  chromogen)  is  decomposed  with  the  lib- 
eration of  indoxyl.  In  herbivorous  animals,  such  as  the 
horse  and  the  rabbit,  the  phenomenon  of  indigouria  is 
said  not  to  be  a  rare  occurrence.  In  the  horse  the  pigment 
consists  of  a  mixture  of  indigo  blue  and  indigo  red,  or 
indirubin,  whereas  in  the  rabbit  the  coloring  matter 
is  indigo  red.  It  is  stated  that  the  occurrence  of  the 
phenomenon  of  indigouria  in  these  herbivorous  animals 
is  not  necessarily  connected  with  any  evidence  of  illness. 
I  believe  there  is  at  present  not  the  slightest  evidence  that 
the  phenomenon  of  indigouria  occurs  in  man  in  a  state  of 
health.  There  seems  to  me  no  evidence  that  indigouria 
depends  on  the  presence  of  free  indoxyl  in  the  blood  and 
urine.  It  is  much  more  likely  that  it  is  a  phenomenon 
dependent  on  the  spontaneous  oxidation  of  indoxyl- 
potassium-sulphate  in  the  urine  in  those  cases  in  which 


274     INFECTIONS  OF  THE  DIGESTIVE  TRACT 

the  quantity  of  this  substance  is  very  extreme.  I 
believe  also  that  the  phenomenon  of  indigouria  never 
arises  except  where  indol  is  being  produced  in  the  intes- 
tine in  uncommonly  large  amounts  and  is  subsequently 
absorbed  in  uncommon  abundance. 


INDIVIDUAL  SUSCEPTIBILITIES  TO  DIFFERENT  ENTEROG- 
ENOUS POISONS  AS  POSSIBLE  FACTORS  IN  DETERMIN- 
ING CLINICAL  TYPES 

Instances  are  many  in  which  clinical  experience  has 
made  it  clear  that  two  persons  of  approximately  the  same 
weight  react  differently  to  the  same  drug,  and  do  so 
regularly.  This  is  true  of  commonly  used  drugs,  such 
as  strychnine,  morphine,  cocaine,  digitalis,  and  antipyrin. 
A  scientific  explanation  of  these  differences  is  for  most 
cases  not  now  possible.  That  they  do  not  depend  on 
gross  differences  in  rapidity  of  absorption  is  shown  in 
the  case  of  some  of  these  drugs  by  the  fact  that  sub- 
cutaneous injections  give  rise  to  the  same  qualitative 
differences.  The  individual  variations  are  to  be  at- 
tributed rather  to  idiosyncrasies  of  the  neuro-muscular 
system  —  the  mechanism  through  which  functional 
derangement  most  readily  finds  expression  in  the  form 
of  symptoms.  The  nervous  system  may  prove  uncom- 
monly susceptible  either  on  account  of  inherent  physico- 
chemical  peculiarities  of  its  constituent  nervous  ele- 
ments or  because  it  is  not  adequately  protected  from  the 
action  of  poisons  by  hepatic  and  other  cells  which  have 
the  power  to  bind,  or  bind  and  oxidize,  or  bind  and  oxi- 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      275 

dize  and  pair,  many  substances  injurious  to  the  nervous 
elements.  An  inherent  susceptibility  of  the  nervous 
elements  themselves  probably  has  its  physical  sub- 
stratum in  side  chains  or  receptors  (according  to  the 
conception  of  Ehrlich)  possessing  affinities  for  sub- 
stances possessing  a  definite  chemical  constitution. 

Of  individual  human  susceptibilities  and  reactions 
to  the  action  of  enterogenous  poisons  almost  nothing 
is  now  known.  Nevertheless  one  cannot  fail  to  recognize 
the  possibility  that  such  individual  susceptibilities  and 
reactions  may  play  an  important  part  in  determining 
the  clinical  manifestations  of  intoxications.  It  is  well 
known  to  clinicians  that  there  are  some  persons  who 
promptly  develop  a  widespread  urticaria  after  indulgence 
in  certain  foods  or  drinks,  as  shellfish  or  strawberries 
or  champagne.  Sir  A.  E.  Wright  tells  me  that  a  patient 
of  his  develops  an  urticarial  eruption  after  ingesting 
organic  acids.  I  had  a  patient  who  suffered  frequent 
urticarial  seizures  attributable  to  somewhat  injudicious 
living.  She  had  marked  indicanuria  and  excessive 
putrefactive  decomposition  in  the  intestinal  tract.  A 
rigid  diet  maintained  more  than  a  year  led  to  a  cessa- 
tion of  the  urticarial  seizures  and  to  a  diminution  in 
the  indican  excreted.  In  a  mood  of  experiment  she  de- 
cided to  test  the  action  of  champagne  and  found  that 
one  glass  was  followed  within  three  hours  by  a  violent 
outbreak  of  general  urticaria.  Here  the  susceptibility 
was  highly  pronounced.  The  urticaria  may  be  connected, 
as  Wright  has  pointed  out,  with  a  diminished  coagu- 
lability of  the  blood,  but  this  is  in  itself  not  a  full  ex- 


276      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

planation  of  the  locally  deranged  function,  since  it  fails 
to  take  account  of  the  nervous  mechanisms  involved  in 
the  localization  of  the  urticarial  wheals. 

In  some  persons  the  indulgence  in  a  single  glass  of 
champagne  is  followed  within  twenty-four  hours  by 
manifestations  of  gout.  In  still  others  champagne 
causes  headache  and  the  excretion  of  increased  amounts 
of  uric  acid.  The  explanation  of  these  different  effects 
is  to  be  sought  in  the  individual  cellular  reactions  of  the 
patient  rather  than  in  the  poison.  There  are  probably 
many  similar  examples  of  individual  susceptibility,  but 
when  we  come  to  study  the  question  in  relation  to  pro- 
cesses found  in  the  digestive  tract  we  cannot  make 
close  comparisons  between  different  persons  because  we 
cannot  say  what  substances  are  being  absorbed.  We 
may  know  that  patients  of  a  certain  group  are  alike  in 
having  intense  indicanuria,  but  we  cannot  say  that  the 
intoxications  may  not  be  different  in  these  cases  owing  to 
differences  with  respect  to  the  absorption  of  other  sub- 
stances than  indol.  Careful  research  may  help  us  to  get 
much  closer  to  the  resemblances  and  differences  in  such 
cases.  In  the  meantime  we  must  content  ourselves  with 
the  suspicion  that  chronic  intoxications  through  the 
absorption  of  similar  quantities  of  the  same  poisons 
produce  different  effects  in  different  persons.  Among 
half  a  dozen  persons  suffering  from  extreme  indicanuria, 
one  suffers  from  headaches  (sometimes  migrain-like), 
another  is  prone  to  lumbago,  another,  perhaps,  has 
epileptic  seizures,  another  mental  depression,  another 
progressive  muscular  atrophy,  and  still  another  suffers 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      277 

from  cyclical  vomiting.  It  would  be  well  worth  while 
to  learn  in  how  far  these  different  manifestations  of 
intoxications  are  dependent  on  common  factors  or  in  how 
far  on  different  agencies.  There  is  good  reason  for 
suspecting  that  very  similar  bacterial  processes  in  the 
digestive  tract  lead  in  one  case  mainly  to  digestive  dis- 
orders and  in  others  (owing  to  a  lesser  sensitiveness  of  the 
digestive  tract  itself)  to  better  absorption  of  poisons  and 
the  development  of  more  remote  consequences  such  as 
gout,  arthritis,  anaemia,  or  nervous  disorders.  While 
it  is  possible  that  these  very  different  manifestations 
are  always  connected  with  different  and  perhaps  spe- 
cifically different  types  of  gastro-enteric  infection  and 
intoxication,  the  possibility  is  not  excluded  that  even 
such  very  different  disorders  may  have  much  in  common 
in  their  etiology. 

That  the  mental  and  emotional  peculiarities  of  indi- 
viduals have  a  large  part  in  fixing  the  type  of  nervous 
reaction  that  occurs  in  consequence  of  intoxications  has 
become  apparent  to  careful  students  of  pathological 
conditions.  It  is  not  unreasonable  to  believe  that  it 
will  well  repay  close  observers  of  the  phenomena  of  dis- 
ease to  take  into  consideration  the  individual  nervous 
reactions  much  more  than  is  at  present  customary. 


TYPES   OF  CHRONIC  EXCESSIVE  INTESTINAL 
PUTREFACTION 

i 

THE  considerable  vacations  in  the  clinical  manifes- 
tations and  pathological  accompaniments  of  chronic 
excessive  intestinal  putrefaction  suggest  that  the  etio- 
logical  conditions  vary  considerably  in  different  cases.  I 
shall  endeavor  in  the  following  pages  to  show  that  there 
are  grounds  for  the  separation  of  different  types  of 
intestinal  putrefactive  processes  and  that  these  grounds 
are  based  on  differences  in  the  character  of  the  putre- 
factive products  and  in  the  bacteria  concerned  with  these 
processes.  The  classification  which  I  offer  is  a  tentative 
one  which  may  in  time  have  to  give  way  to  one  founded 
on  a  fuller  knowledge  of  the  significant  intestinal  con- 
ditions than  we  at  present  possess.  In  any  event  it 
must  undergo  modification.  It  is,  however,  proposed 
here  in  the  belief  that  it  will  serve  a  useful  purpose  in 
helping  to  classify  cases  of  disease  and  in  giving  direction 
to  systematic  study. 

It  is  a  striking  fact  that  while  many  cases  of  excessive 
intestinal  putrefaction  are  associated  with  the  presence 
of  indican  in  the  urine  in  large  amount,  there  are  other 
cases  of  considerable  gravity  clinically  which  fail  to 
show  much  indican  in  the  urine  or  may  indeed  be  entirely 
free  from  indicanuria  during  a  long  period  of  observa- 
tion. I  propose  to  divide  cases  of  chronic  excessive 

278 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      279 

intestinal  putrefaction  into  those  which  show  an  exces- 
sive indicanuria  and  those  which  do  not.  The  proposed 
classification  recognizes  three  types  of  putrefaction  which 
are  common :  the  first  may  be  called  the  Indolic  Type, 
and  is  characterized  by  indicanuria  dependent  chiefly 
upon  excessive  decomposition  induced  through  the  co- 
operation of  members  of  the  B.  coli  group  (and  probably 
B.  putrificus) ;  the  second  type  of  intestinal  putrefaction 
may  be  designated  the  Saccharo-butyric  Type,  and  is 
initiated  especially  by  anaerobic  organisms  in  the  digest- 
ive tract.  In  its  simplest  form  it  is  associated  with 
very  little  production  of  indol  in  the  intestinal  tract 
and  hence  with  slight  indicanuria  or  even  an  entire 
absence  of  indican  from  the  urine.  In  the  third  group 
of  cases  we  find  associated  the  characters  of  the  indolic 
and  the  saccharo-butyric  types  of  decomposition.1  I 
will  describe  these  types  briefly  according  to  my 
present  conception  of  their  etiology  and  pathological 
characters. 

1 1  think  it  will  become  desirable  to  distinguish  a  skatolic  type 
of  putrefactive  decomposition,  i.e.  a  condition  in  which  the  in- 
testinal bacteria  persistently  form  skatol  in  amounts  in  excess 
of  the  indol  made.  As  mentioned  in  speaking  of  skatol,  I  have 
found  this  product  of  decomposition  abundant  and  dominant 
over  indol  only  under  conditions  of  clinical  deviation  from  normal 
standards.  But  as  I  am  still  in  doubt  as  to  the  bacterial  conditions 
that  determine  skatol  production,  I  hesitate  at  present  to  make 
skatol  prominent  in  a  plan  of  classification.  Moreover,  I  do  not 
yet  know  whether  excessive  skatol  production  corresponds  to 
characteristic  manifestations. 


280      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

I.    THE   INDOLIC   TYPE   OF   EXCESSIVE   INTESTINAL 
PUTREFACTION 

It  has  already  been  stated  that  there  is  some  reason 
for  believing  that  organisms  of  the  B.  coli  type  which 
are  capable  of  forming  indol  abundantly  may  invade  the 
small  intestine  and  there  give  rise  to  bacterial  cleavages 
which  largely  replace  the  normal  try p tic  digestion.  The 
proof  that  the  small  intestine  is  invaded  by  some  variety 
of  indol-producing  colon  bacilli  in  cases  of  marked  indi- 
canuria  is  still  lacking,  for  the  reason  that  it  is  ordinarily 
impossible  to  obtain  evidence  on  this  point  from  a  living 
subject,  whereas  postmortem  studies  with  reference  to 
this  point  are  open  to  criticism  on  account  of  the  rapid 
wandering  of  the  colon  bacilli  which  occurs  after  death. 
Of  all  the  organisms  of  the  digestive  tract  which  we  have 
individually  studied,  we  have  found  none  that  will  make 
a  larger  amount  of  indol  than  certain  strains  of  colon 
bacilli  when  grown  on  peptone  bouillon.  There  are, 
moreover,  cases  of  excessive  intestinal  putrefaction  in 
which  the  dominant  organism  in  the  intestinal  tract  (if 
we  may  judge  from  the  material  obtained  through  the 
use  of  cathartics)  is  some  variety  of  colon  bacilli.  In  such 
cases,  the  anaerobes  of  the  intestine  may  be  present  in 
very  small  numbers,  so  that  it  seems  safe  to  exclude 
them  from  a  significant  part  hi  the  formation  of  putre- 
factive products.  It  seems  reasonable  hi  these  cases 
to  attribute  the  formation  of  indol  to  an  unusual  activity 
on  the  part  of  the  colon  bacilli.  There  are,  perhaps,  also 
instances  in  which  the  presence  of  an  indol-producing 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      281 

proteus  organism  is  a  factor.  But  I  am  not  inclined 
to  ascribe  great  importance  to  the  proteus  organism  in 
this  connection,  for  aerobic  liquefiers  of  gelatin  have 
generally  been  lacking  or  few  in  number.  If  we  assume 
that  the  indol  produced  in  these  cases  of  indicanuria  is 
made  largely  though  the  action  of  colon  bacilli/  we  are 
brought  to  the  question,  In  what  part  of  the  intestinal 
tract  does  the  indol  production  chiefly  occur  ?  We  know 
that  the  colon  bacilli  have  only  a  very  feeble  action  upon 
native  proteids  such  as  are  used  for  food.  We  are  there- 
fore forced  to  the  conclusion  that  the  indol  produced  by 
the  colon  bacilli  must  have  been  formed  through  the 
cooperative  agency  of  the  digestive  juices  or  putrefac- 
tive bacteria.  The  anaerobic  putrefactive  bacteria 
may  be  excluded  from  the  present  discussion,  since  the 
cases  here  in  question  are  those  in  which  these  bacteria 
are  present  in  only  very  small  numbers  in  the  digestive 
tract.2  So  we  have  to  fall  back  on  the  pro teoly zing  action 
of  the  digestive  juices  to  explain  that  preparation  of  the 
proteid  food  which  is  necessary  for  a  successful  attack 
by  organisms  of  the  B.  coli  type.  Where  only  a  moder- 
ate amount  of  food  is  being  used,  and  this  in  a  form 
readily  digested  and  absorbed,  such  as  egg-white  or 
milk,  it  is  unreasonable  to  suppose  that  the  foodstuff 

1 1  am  confident  that  an  indol-making  strain  of  B.  putrificus  is 
sometimes  an  important  agent  in  establishing  indicanuria,  but  do 
not  know  any  instance  where  the  influence  of  colon  bacilli  could  be 
excluded. 

2 1  have  noticed  that  certain  Gram-positive  diplococci  from  the 
small  intestine  peptonize  casein  with  moderate  rapidity,  and  it  is 
possible  that  such  organisms,  when  excessive,  prepare  the  way  for 
the  putrefactive  action  of  colon  bacilli. 


282      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

is  attacked  by  the  colon  bacilli  mainly  in  the  large  in- 
testine. It  seems  more  legitimate  to  assume  that  they 
are  attacked  in  the  small  intestine  in  the  manner  already 
mentioned.  It  is,  of  course,  likely  that  in  some  cases 
hydrolyzed  proteids  find  their  way  into  the  ileum  and 
large  intestine,  and  here  it  is  necessary  to  assume  that 
the  colon  bacilli  have  migrated  upward  from  their  usual 
habitat  in  order  to  explain  the  phenomenon  of  excessive 
indican  production.  I  may  mention  an  illustration  of 
the  indolic  type  of  excessive  intestinal  putrefaction.  The 
patient  was  a  lady  seventy-five  years  of  age  who  had  the 
peculiarity  of  having  lived  since  childhood  on  a  diet 
consisting  almost  exclusively  of  potatoes,  hominy,  and 
bread,  and  from  which  meat  had  been  rigorously  excluded. 
She  ate  little  food,  but  was  well  nourished  and  uncom- 
monly robust.  .  She  ultimately  fell  ill  from  a  subacute 
gastro-enteric  disturbance  in  which  there  was  loss  of 
appetite,  irregularity  of  the  bowels,  and  some  signs  of 
gastritis.  The  faeces  at  this  time  showed  fields  consisting 
mainly  of  Gram-negative  bacilli  mostly  of  the  B.  coli 
type.1  These  fields  contained  extremely  few  putrefac- 
tive anaerobes.  Nevertheless  the  urine  contained  ex- 
ceptionally large  quantities  of  indican,  and  this  was 
apparently  a  persistent  feature. 

The  indolic  type  of  chronic  excessive  intestinal  putre- 
faction is  common  in  cases  of  complete  or  partial  occlu- 
sion of  the  common  bile  duct  with  or  without  jaundice, 

1  Two  kinds  of  colon  bacilli  and  a  positive  diplococcus  were  iso- 
lated by  Mr.  Ward.  One  of  these  strains  of  colon  bacilli  was  a 
strong  indol  maker. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      283 

and  is  probably  a  common  association  of  functional  pan- 
creatic achylia,1  a  state  which  is  probably  not  uncommon. 
Some  of  the  most  pronounced  instances  of  indicanuria 
with  which  I  have  met  have  been  in  cases  of  organic 
structural  occlusion  of  the  common  duct.  There  must 
be  in  these  cases  a  great  diminution  in  the  proteolytic 
action  of  the  intestinal  digestive  juice,  and  putrefactive 
cleavages  are  doubtless  due  very  largely  to  the  action  of 
bacteria  and  especially  the  colon  bacilli.  I  have  noticed 
in  several  cases  of  jaundice  that  the  fseces  held  mainly 
Gram-negative  organisms  of  the  B.  coli  type.  In  some 
autopsies  such  organisms  have  been  dominant  through- 
out the  digestive  tract.  Bacteriological  studies  for  the 
identification  of  the  organisms  and  their  biochemical 
characters  in  such  cases  have  not  yet  been  made.  I  men- 
tion these  appearances,  however,  as  being  of  interest 
in  the  present  connection,  since  they  were  characterized 
by  the  absence  of  putrefactive  anaerobes  in  more  than 
very  small  numbers.  In  some  instances  cultural  obser- 
vations on  the  mixed  faecal  flora  have  borne  out  the  view 
that  the  colon  bacilli  were  the  dominant  type  and  the 
putrefactive  anaerobes  were  few  in  number. 

Occlusions  of  the  small  intestine  are  almost  invariably 
followed  by  intense  indicanuria  even  when  the  occlu- 
sion is  in  the  jejunal  region.  The  bacteriological  ex- 
planation in  such  cases  is  not  clear.  The  reversal  of 
peristalsis,  above  the  level  of  obstruction,  must  serve 
to  distribute  colon  bacilli  from  the  ileum  or  jejunum 

1  A.  Schmidt,  "  Functionelle  Pankreasachylie,"  Deutsch.  Archiv 
/.  klin.  Med.,  Ixxxvii,  p.  456,  1906. 


284      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

throughout  the  small  intestine,  between  the  stomach 
and  the  obstruction.  This  dissemination  of  colon 
bacilli  above  the  occlusion  may  be  an  important  factor 
in  favoring  indol  production.  Where  the  obstruction 
lies  high,  as  in  the  upper  jejunum,  indicanuria  is  said 
not  to  occur. 

The  development  of  a  complete  obstruction  of  the 
small  intestine  is  followed  by  obstinate  constipation, 
and  this  may  influence  the  putrefactive  conditions  below 
the  obstruction.  But  I  have  already  mentioned  that 
mere  constipation  does  not  necessarily  lead  to  indican- 
uria. On  this  account  it  is  difficult  to  determine  the  part 
played  by  bacterial  conditions  below  the  obstruction,  in 
contributing  to  the  formation  of  indol.  It  appears,  on 
the  whole,  that  it  is  mainly  the  bacterial  conditions  above 
the  obstruction  that  determine  the  presence  or  absence 
of  an  extreme  indicanuria.  This  view  is  not  inconsistent 
with  the  fact  that  indicanuria  may  persist  after  the  small 
intestine  has  been  emptied  of  food  through  repeated 
vomiting,  for  it  is  known  that  indol  often  continues  to 
be  found  in  the  digestive  tract  of  starving  animals. 
Small  quantities  of  proteid  (perhaps  derived  mainly  from 
desquamated  epithelial  cells)  apparently  suffice  to  insure 
indol  formation  when  the  bacterial  conditions  are  favor- 
able. 

A  well-marked  group  of  cases  which  may  provisionally 
be  classed  with  the  simple  indolic  type  is  that  which 
may  be  characterized  as  the  marantic,  large-belly  type 
of  chronic  intestinal  indigestion  in  children.  This 
condition  has  long  been  known  to  clinicians  as  an 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      285 

extremely  obstinate  form  of  digestive  derangement,  mani- 
festing itself  in  a  distinct  retardation  of  growth  (usually 
without  much  mental  retardation),  in  distension  of  the 
abdomen  by  gas,  flatulence,  intolerance  of  carbohydrates, 
and  voluminous,  light-colored,  usually  gray  and  fatty 
stools  containing  much  gas.  In  many  of  these  children 
there  is  excessive  sweating  of  the  head.  I  have  studied 
with  considerable  care  several  children  corresponding  to 
this  clinical  type  (most  of  them  patients  of  Professor  L.  E. 
Holt,  who  has  in  every  way  aided  me  in  the  effort  to 
learn  something  about  the  underlying  conditions  present 
in  this  striking  derangement).  It  was  found  that  it  is 
a  characteristic  in  these  cases  that  the  urine  contains 
a  large  amount  of  indican  and  usually  an  excessive 
amount  of  phenol.  The  phenol  may  amount  to  more 
than  one  hundred  milligrams  in  twenty-four  hours,  in  the 
urine  from  a  child  not  more  than  three  or  four  years  of 
age.  The  Ehrlich  aldehyde  reaction  of  the  urine  may  or 
may  not  be  excessive.  After  a  long  period  of  careful  diet- 
ing in  which  carbohydrates  are  very  much  restricted  the 
indican  may  disappear  from  the  urine  in  such  cases 
although  the  patients  show  but  little  gain  in  weight  or 
strength.  This  falling  off  in  indican  of  the  urine  is  to 
be  regarded  as  a  favorable  indication  and  often  precedes 
by  many  months  more  obvious  clinical  indications  of 
recovery.  In  some  instances,  however,  there  occurs  a 
slow  gain  in  strength  and  in  weight  and  in  the  ability 
to  digest  carbohydrate  food  despite  the  fact  that  the 
improvement  in  the  excretion  of  indican  and  phenol  is 
only  slight.  Under  the  most  favorable  circumstances 


286       INFECTIONS  OF  THE  DIGESTIVE  TRACT 

improvement  is  very  slow,  and  slight  errors  in  diet  are 
followed  by  prompt  reappearance  of  flatulence  and  per- 
haps diarrhoea.  Fats  and  proteids  are  well  tolerated. 

A  feature  in  this  form  of  chronic  excessive  intestinal 
putrefaction  is  the  readiness  with  which  fatigue  comes 
on.  A  child  of  six  or  eight  years  of  age  will  show  fatigue 
after  a  very  short  walk  and  will  manifest  a  want  of  in- 
terest in  exercise  and  play.  There  is  in  fact  a  state  of 
chronic  fatigue,  which  I  attribute  to  the  absorption  of 
putrefactive  products.  If  the  trouble  comes  on  during 
infancy,  there  may  be  considerable  delay  in  the  develop- 
ment of  the  ability  of  the  child  to  stand  and  walk  without 
support,  and  a  child  of  five  or  six  years  or  over  may  be 
unable  to  go  upstairs  except  by  a  kind  of  creeping 
motion.  A  certain  emotional  irritability  is  common  in 
these  children.  As  a  rule  they  are  not  much  retarded 
mentally  except  in  so  far  as  they  have  missed  opportuni- 
ties for  conventional  learning.  On  the  contrary,  one  not 
infrequently  is  struck  by  the  contrast  between  the  sharp 
wits  of  these  children  and  their  physical  retardation. 

The  ethereal  sulphates  are  regularly  increased  in  the 
urine  in  cases  of  the  kind  under  consideration,  that  is  to 
say,  there  is  not  merely  a  relative  increase  of  the  ethereal 
as  compared  with  the  preformed  sulphates,  but  usually 
also  an  actual  excess  in  the  absolute  amount  of  the 
ethereal  sulphates.  The  proportion  of  ethereal  to  pre- 
formed sulphates  may  be  one  to  seven,  or  one  to  five, 
or  even  one  to  four.  It  can  usually  be  shown  that  the 
stools  contain  considerable  quantities  of  indol  and  phenol. 

A  noteworthy  peculiarity  of  these  cases  is  the  presence 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      287 

of  a  very  large  proportion  of  Gram-positive  bacilli  cor- 
responding closely  to  the  morphology  of  the  organism 
described  by  Tissier  as  B.  bifidus.  It  has  already  been 
pointed  out  that  the  fseces  of  breast-fed  children  consist 
very  largely  of  Gram-positive  organisms  of  the  bifidus 
kind.  When  children  reach  the  age  of  three  or  four 
years,  the  bifidus  bacilli  are  usually  comparatively  few 
in  number  and  the  dominant  type  is  some  form  of  colon 
bacillus.  In  children  from  four  to  ten  years  of  age  the 
Gram-negative  bacilli  of  the  colon  type  are  much  in 
excess  normally  as  compared  with  the  organisms  repre- 
sentative of  bifidus.  In  the  cases  of  chronic  intestinal 
indigestion  which  are  under  consideration  I  have  met 
with  a  great  preponderance  of  bifidus-like  organisms  in 
children  as  old  as  seven  or  eight  years.  The  cultural 
proof  that  the  organisms  to  which  I  refer  are  in  reality 
the  same  as  those  normally  present  in  the  faeces  in  in- 
fancy is  lacking,  as  I  have  been  unable  to  adequately 
study  the  biochemical  characters  of  these  organisms. 
In  sugar-bouillon  fermentation  tubes,  however,  the 
resemblance  is  a  very  close  one ;  that  is  to  say,  the  growths 
observed  in  lactose  or  dextrose  bouillon  show  many 
instances  of  the  bifid  form  of  bifidus  and  also  many 
instances  of  so-called  punctate  forms  in  which  Gram- 
positive  portions  of  the  bacillus  alternate  with  segments 
of  the  cell  body  which  fail  to  take  the  Gram-stain.  As- 
sociated with  these  bifidus  forms  in  the  faeces  of  the 
marantic  cases  one  finds  moderate  numbers  of  colon 
bacilli,  or  colon  bacilli  may  be  wholly  absent  from  the 
fields.  In  the  lactose-bouillon  fermentation  tubes  one 


288      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

may  find  excessive  numbers  of  positive  diplococci.  It 
should  be  especially  noted  that  the  common  anaerobic 
putrefactive  organisms  are  present  in  very  small  num- 
bers. It  is  not  certain  that  the  bifidus-\ike  organisms 
found  in  these  cases  of  chronic  indigestion  in  children 
represent  the  preponderance  of  a  type  which  should, 
under  normal  conditions,  gradually  be  replaced  by  colon 
bacilli,  but  the  idea  is  one  which  forces  itself  strongly 
upon  one.  It  is  possible  that  the  organism  may  have 
acquired  other  characters  than  those  pertaining  to  the 
bifidus  bacilli  of  the  nursling. 

Associated  with  the  Gram-positive  bifidus-\ike  or- 
ganisms in  the  faces  one  may  find  moderate  numbers 
of  positive  diplococci  or  short  streptococcal  chains. 
These  diplococci  may  appear  in  considerable  abundance 
in  the  fermentation  tubes  or  may  give  rise  there  to  an 
abundance  of  streptococcus  forms.  In  one  apparently 
typical  case  which  was  under  observation  for  a  long  time, 
the  child  at  the  height  of  the  disease  (when  indicanuria 
was  very  marked)  showed  in  the  faecal  fields  considerable 
numbers  of  these  Gram-positive  diplococci.  After  a 
period  of  six  months,  upon  a  strict  proteid  and  fat  diet, 
the  diplococci  were  no  longer  present  in  the  fields.  It 
was  also  noticeable  that  indican  had  disappeared  from 
the  urine  although  the  patient  had  gained  very  little  in 
weight  and  strength. 

Whether  in  these  cases  the  production  of  indol  is  due 
to  the  colon  bacilli  present  in  the  upper  part  of  the  tract 
or  whether  it  is  due  in  part  to  other  types  of  organisms 
is  by  no  means  clear.  B.  bifidus  in  these  cases  certainly 


INFECTIONS  OF  THE  DIGESTIVE  TRACT     289 

does  not  occupy  the  entire  intestinal  tract,  as  may  be 
shown  in  diarrhoeal  stools  which  contain  colon  bacilli 
as  well  as  B.  bifidus.  It  is  uncertain  in  how  far  the  re- 
tardation in  growth  and  the  myasthenia  which  are 
characteristic  of  these  cases  are  explicable  through  the 
intoxication  induced  by  the  absorption  of  excessive 
quantities  of  indol  or  phenolic  substances.  I  am  dis- 
posed to  think  these  bodies  are  an  important  factor  in 
determining  the  undue  fatigue.  The  retardation  in 
growth  may  have  hi  part  a  similar  origin,  but  it  is  prob- 
able that  this  is  partly  the  effect  of  a  failure  of  the  or- 
ganism to  utilize  food  normally,  owing  to  the  excessive 
decompositions  that  occur  in  the  intestinal  tract.  No 
matter  how  much  food  is  given,  the  excessive  bacterial 
changes  rob  the  organism  of  enough  caloric  potential 
to  make  normal  growth  impossible. 

In  the  treatment  of  these  cases  it  is  necessary  to  be 
patient.  It  is  essential  to  improve  the  character  of  the 
digestive  processes  before  one  can  reasonably  hope  to 
secure  a  gain  in  weight  and  strength.  Carbohydrates 
should  be  permitted  in  only  very  small  amount  and 
chiefly  in  the  form  of  well-cooked  rice  or  hominy  or 
Huntley  and  Palmer's  breakfast  biscuits.  It  may  be 
advantageous  for  a  time  to  peptonize  the  milk  in  order  to 
secure  early  absorption.  Moderate  quantities  of  chicken 
or  beef  or  mutton  may  be  permitted,  but  all  meat  should 
be  given  in  a  finely  divided  form.  It  sometimes  has 
seemed  best,  in  children  as  old  as  five  or  six  years  of  age, 
to  allow  only  two  meals  in  the  course  of  the  day,  these 
being  rather  generous.  It  is  helpful  to  practice  high  irri- 


290      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

gation  in  order  to  avoid  as  far  as  possible  putrefactive 
decompositions  in  the  large  intestine.  A  great  deal  of 
rest  is  necessary  for  these  children  and  they  should  not 
be  permitted  to  play  or  walk  to  the  point  of  fatigue. 
Patients  of  the  class  under  consideration  often  do  badly 
in  cold  weather,  probably  because  they  cannot  afford 
the  caloric  loss  to  which  they  are  then  subjected.  Where 
this  is  the  case  a  period  of  residence  in  a  mild  winter 
climate  is  helpful.  Improvement  is  sometimes  so  slow 
that  every  one  concerned  with  the  case  may  become  dis- 
couraged, but  it  is  certain  that  a  high  degree  of  improve- 
ment can  occur  even  after  several  years  of  extremely 
slow  progress.  I  have  several  times  known  this  to  be 
the  case.  In  order  to  secure  this  improvement,  however, 
it  is  impossible  to  make  concessions  in  regard  to  diet,  and 
the  policy  of  largely  excluding  carbohydrates  must  be 
enforced.  It  cannot  be  denied  that  even  in  those  cases 
where  the  best  results  are  obtained  there  is  commonly 
a  retardation  in  growth  which  is  still  manifest  at  the 
time  of  puberty.  Moreover,  there  is  no  doubt  that  per- 
sons who  have  suffered  from  the  conditions  under  consid- 
eration during  the  period  of  childhood  become  especially 
susceptible  to  intestinal  disorders  in  later  years  and  sel- 
dom attain  robust  health.  There  are  probably  many 
persons  in  the  community  whose  digestive  derangements 
date  from  early  life,  and  in  many  of  these  cases  the  less 
pronounced  forms  of  the  type  of  chronic  intestinal  indi- 
gestion which  has  just  been  described  have  doubtless 
constituted  the  foundation  of  invalidism  in  adult  life. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      291 

H.     THE    SACCHARO-BUTYRIC    TYPE    OF    CHRONIC   EXCES- 
SIVE   INTESTINAL   PUTREFACTION 

This  form  of  intestinal  derangement  is  characterized 
by  a  chronic  putrefactive  process  (having  its  seat  mainly 
in  the  large  intestine  and  lower  ileum)  and  due  to  the 
action  of  very  large  numbers  of  strictly  anaerobic 
butyric-acid-producing  bacteria  capable  of  multiplying 
by  means  of  spore  formation.  A  thorough  study  of  the 
anaerobes  concerned  with  this  type  of  decomposition 
has  not  yet  been  made,  but  it  may  confidently  be  stated 
that  the  organism  most  prominently  concerned  in  at 
least  a  large  number  of  the  cases  is  B.  aerogenes  capsu- 
latus  (B.  Welchii).  The  characters  of  this  organism 
have  already  been  elsewhere  described.  Associated 
with  B.  aerogenes  capsulatus  may  be  found  B.  putrificus 
and  possibly  in  some  cases  the  bacillus  of  malignant 
oedema.  In  many  cases,  however,  B.  putrificus  has  not 
been  found  in  the  fermentation  tubes  or  in  the  flasks 
containing  various  media  into  which  suspensions  of 
the  mixed  faecal  flora  have  been  inoculated.  Anaerobic 
plates  made  from  the  suspensions,  heated  for  twenty 
minutes  to  80°  C.,  have  shown  B.  aerogenes  capsulatus  to 
be  the  dominant  or  even  the  exclusive  strict  anaerobe 
growing  upon  sugar-blood  agar  or  blood  agar.  In  a 
certain  proportion  of  cases  the  fsecal  fields  have  shown 
B.  aerogenes  capsulatus  to  be  associated  with  large 
numbers  of  Gram-positive  diplococci,  and  these  Gram- 
positive  diplococci  have  been  grown  very  abundantly 
in  the  fermentation  tubes;  that  is,  they  have  assumed  a 


292      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

prominence  there  which  is  not  often  observed  in  the  case 
of  persons  in  good  health.  It  seems  not  improbable 
that  the  presence  of  these  diplococci  are  of  importance 
to  the  process,  but  their  precise  relation  to  it  cannot  be 
at  present  confidently  stated.  In  some  instances  these 
Gram-positive  diplococci  appear  in  the  fermentation 
tubes  in  great  abundance,  although  they  are  not  seen 
in  the  faecal  fields  in  such  number  as  to  attract  special 
attention. 

A  very  common  phenomenon  in  cases  of  the  saccharo- 
butyric  type  of  chronic  excessive  intestinal  putrefaction 
is  the  formation  of  only  small  volumes  of  gas  in  sugar- 
bouillon  fermentation  tubes  after  these  have  been  inocu- 
lated with  the  mixed  faecal  flora.  As  already  explained, 
it  has  been  our  custom  in  routine  work  to  study  the 
gas  production  on  four  sugar-bouillon  tubes  containing 
dextrose  bouillon,  levulose  bouillon,  saccharose  bouillon, 
and  lactose  bouillon.  The  gas  production  in  these 
tubes  has  often  fallen  to  one-half  that  observed  ordinarily 
in  health,  and  the  volume  may  even  fall  to  one-quarter 
or  one-fifth  the  total  gas  production  observed  under 
normal  conditions.  In  a  few  cases  some  of  the  fermen- 
tation tubes  have  contained  no  measurable  amount  of 
gas.  This  is,  however,  an  exceptional  condition.  The 
explanation  of  this  phenomenon  of  small  gas  production 
in  the  fermentation  tubes  appears  to  lie  in  the  diminu- 
tion hi  the  number  of  living  organisms  of  the  B.  coli 
type  that  are  present  in  the  faeces.  That  the  colon 
bacilli  are  much  reduced  in  numbers  is  evident  in  some 
of  the  cases  of  saccharo-butyric  putrefaction  from  the 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      293 

microscopical  examination  of  the  Gram-stained  faecal 
fields,  even  in  fields  from  diarrhceal  stools.  It  is  pos- 
sible that  in  some  of  the  cases  that  have  come  under 
observation  the  typical  colon  bacilli  have  been  replaced 
by  some  allied  form  of  Gram-negative  organism  capable 
of  forming  less  gas  than  is  ordinarily  found  as  the  prod- 
uct of  normal  colon  bacilli  on  sugar  bouillon.  We  have 
not  yet  had  an  opportunity  to  make  a  careful  study 
of  our  cases  of  saccharo-butyric  putrefaction  from  the 
standpoint  of  the  characters  of  the  colon  bacilli  present. 

While  the  reduction  in  the  total  number  of  living  colon 
bacilli  has  been  shown  to  exist  in  many  of  our  cases  of 
saccharo-butyric  putrefaction  by  means  of  plating  on 
litmus  gelatin,  there  are  exceptional  instances  in  which 
there  is  no  evidence  that  the  number  of  colon  bacilli 
has  been  reduced.  The  evidence,  however,  in  these 
cases  is  confined  to  the  appearance  of  acid-forming 
colonies  on  litmus  gelatin  and  agar  and  to  the  occur- 
rence of  normal  gas  production  in  the  fermentation 
tubes. 

The  presence  of  large  numbers  of  putrefactive  anae- 
robes in  the  intestinal  tract  and  especially  of  B.  aero- 
genes  capsulatus,  gives  to  the  intestinal  contents  a  pecul- 
iar character.  These  organisms,  as  already  mentioned, 
are  capable,  under  anaerobic  conditions,  of  attacking 
carbohydrates  and  proteids  in  a  vigorous  manner.  In 
either  case  there  is  a  formation  of  butyric  acid,  often  in 
considerable  amount.  This  may  be  associated  with  the 
production  of  propionic,  caproic,  or  valeric  acids.  The 
odor  of  the  movements  from  patients  in  whom  this 


294      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

form  of  putrefaction  is  pronounced  is  often  intense  and 
characteristic,  suggesting  butyric  or  caproic  acid.  When 
proteids  are  attacked  by  B.  aerogenes  capsulatus  there  is 
not  only  a  production  of  butyric  acid,  but  also  a  libera- 
tion of  gas,  although  there  is  less  gas  liberated  than  when 
the  organisms  attack  carbohydrates.  The  gas  liberated 
consists  in  part  of  hydrogen  and  in  part  of  carbon 
dioxide.  Perhaps  some  methane  is  also  formed.  As  a 
result  of  the  excessive  production  of  gas  the  faeces  have 
a  low  specific  gravity  and  float  on  the  surface  of  water. 
Frequently  small  bubbles  of  gas  may  be  seen  to  be 
liberated.  The  presence  of  considerable  quantities  of 
gas  in  the  form  of  small  bubbles  in  the  intestinal  contents 
contributes  to  give  them  a  light  color.  Another  factor 
which  enters  into  the  light  color  often  observed  in  the 
faeces  in  cases  of  saccharo-butyric  putrefaction  is  a  re- 
duction of  bilirubin  and  other  coloring  matters  by  the 
anaerobic  bacteria.  Reducing  processes  normally  go 
on  in  the  intestinal  tract  but  they  are  usually  of  moder- 
ate intensity  in  conditions  of  health.  In  excessive  sac- 
charo-butyric putrefaction,  on  the  contrary,  the  processes 
of  reduction  are  extremely  active,  owing  doubtless  largely 
to  the  liberation  of  free  hydrogen.  The  faeces  of  cases 
of  saccharo-butyric  putrefaction  when  subjected  to  an 
appropriate  oxidizing  agent,  such  as  mercuric  chloride 
in  concentrated  solution,  usually  give  a  strong  pink  or 
red  color  which  is  rendered  more  striking  when  the 
material  which  has  already  been  reddened  in  this  way  is 
thrown  into  water,  which  then  dissolves  out  the  newly 
formed  coloring  matter  and  reveals  its  intensity.  This 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      295 

reaction  is  probably  due  to  the  presence  of  an  excessive 
amount  of  hydrobilirubin. 

In  consequence  of  the  presence  of  the  higher  fatty 
acids  in  the  faeces  in  considerable  amount,  there  may  be 
imparted  to  the  contents  of  the  lower  bowel  a  slight  acid 
reaction.  The  reaction,  however,  may  be  neutral  or 
even  alkaline.  The  fatty  acids  in  question  are  neutral- 
ized by  bases  formed  in  the  course  of  putrefactive 
processes  and  especially  by  ammonia,  ammonium  buty- 
rate  sometimes  being  formed  in  considerable  amount. 
It  is  probable  that  the  production  of  ammonium  buty- 
rate  in  excessive  amount  acts  as  an  irritant  to  the  in- 
testinal tract  and  may  be  the  cause  of  a  certain  softness 
of  the  movements  1  in  cases  of  excessive  saccharo-butyric 
putrefaction  or  may  even  be  responsible  for  a  diarrhoaal 
condition.  It  is,  however,  not  clear  that  this  is  the  sole 
cause  of  such  evidence  of  irritation,  as  other  irritative 
products  may  be  associated  with  ammonium  butyrate. 

The  faeces  in  the  condition  under  consideration  usually 
show  the  presence  of  little  or  no  indol.  Indol  may  be 
wholly  absent.  More  commonly  there  is  a  small  amount 
of  indol,  —  perhaps  two  or  three  milligrams  in  one  hun- 
dred grams  of  the  intestinal  contents.  The  quantity  of 
phenol  may  be  slightly  in  excess  of  that  normally  found, 
but  this  is,  I  think,  not  usually  the  case.  In  con- 
sequence of  the  small  absorption  of  indol  the  urine  con- 

1  The  consistence  of  the  stools  may  be  influenced  by  the  liquefy- 
ing action  of  the  anaerobes  on  proteids.  A  normal  stool  may 
stand  in  the  laboratory  for  days  without  changing  in  consistency; 
a  stool  containing  a  great  excess  of  putrefactive  anaerobes  may 
spontaneously  liquefy  in  the  course  of  a  week. 


296      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

tains  little  or  no  indican.  The  cases  in  which  large 
quantities  of  indican  are  found  in  the  urine  must  be 
regarded  as  belonging  in  a  different  category  from  the 
cases  which  are  now  under  discussion.  But  it  must  be 
admitted  that  a  patient  may  show  considerable  ^changes 
in  regard  to  the  indol  production;  a  person  who  at  one 
time  produces  little  intestinal  indol  will  at  other  times 
produce  a  considerable  amount.  Although  the  indican 
of  the  urine  is  usually  small  or  may  be  wholly  absent, 
the  ethereal  sulphates  are  often  somewhat  in  excess. 
The  explanation  of  this  fact  is  not  clear.  It  indicates 
that  other  putrefactive  products  than  indol  have  been 
absorbed  from  the  intestine  and  have  paired  with  sul- 
phuric acid.  In  some  cases  perhaps  phenolic  bodies  are 
responsible  for  the  increase  in  the  ethereal  sulphates, 
but  I  have  observed  cases  in  which  the  increase  in  the 
ethereal  sulphates  appeared  to  me  to  be  out  of  propor- 
tion to  the  amount  of  phenol  recoverable  from  the  urine. 
It  is  quite  possible  that  substances  heretofore  over- 
looked have  been  largely  responsible  for  the  increase  of 
ethereal  sulphates  observed.  There  are,  however,  cases 
of  excessive  saccharo-butyric  putrefaction  in  which  one 
cannot  say  that  the  ethereal  sulphates  are  in  excess. 

Of  the  formation  of  sulphur  compounds  hi  the  intesti- 
nal tract  during  the  process  of  saccharo-butyric  putre- 
faction little  is  yet  known.  There  is  no  evidence  that 
hydrogen  sulphide  is  produced  in  excessive  amount  in 
these  cases.  As  regards  the  formation  of  mercaptan, 
the  evidence  is  against  the  view  that  anything  more 
than  a  trace  of  methyl  mercaptan  is  liberated  from  the 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      297 

putrefying  material  in  the  intestine,  but  it  must  be  ad- 
mitted that  the  facts  bearing  on  this  point  are  not  con- 
clusive. Outside  the  body  the  mixed  fsecal  flora  from 
cases  of  excessive  saccharo-butyric  putrefaction  is  usu- 
ally capable  of  forming  mercaptan  on  peptone  bouillon 
and  in  some  cases  the  amount  produced  hi  twenty-four 
hours  is  sufficient  to  give  a  very  strong  reaction  in  the 
isatin-sulphuric-acid  tube.  This  condition  is  unphysio- 
logical,  as  it  is  not  observed  in  most  adults  in  good 
health.  A  moderate  mercaptan  reaction  is  often  ob- 
tained, as  already  stated,  through  the  action  of  the 
mixed  fsecal  flora  derived  from  apparently  healthy 
young  children.  That  the  reaction  is  abnormal  is 
shown  not  merely  by  the  infrequency  of  its  occurrence 
in  healthy  adults,  but  also  by  the  fact  that  a  patient 
when  improving  from  conditions  of  marked  saccharo- 
butyric  putrefaction  will  usually  lose  the  flora  capable 
of  making  methyl  mercaptan  in  peptone  bouillon.  A 
satisfactory  explanation  of  the  formation  of  methyl 
mercaptan  by  the  mixed  fsecal  flora  cannot  yet  be  offered. 
It  is  easy  to  show  that  B.  putrificus  is  able  to  form  methyl 
mercaptan,  and  in  some  cases  of  saccharo-butyric  pu- 
trefaction B.  putrificus  occurs  abundantly,  especially  in 
peptone  bouillon  to  which  has  been  added  magnesium 
or  calcium  carbonate.  In  such  instances  it  would 
appear  that  the  methyl  mercaptan  is  formed  as  a  result 
of  the  activity  of  B.  putrificus.  There  are  other  cases, 
however,  in  which,  although  methyl  mercaptan  is 
formed  by  the  mixed  fsecal  flora,  one  fails  to  obtain 
B.  putrificus,  and  hence  the  reaction  cannot  confidently 


298      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

be  ascribed  to  the  presence  of  this  organism.  I  think 
it  probable  that  B.  aerogenes  capsulatus  is  sometimes 
capable  of  making  methyl  mercaptan,  but  apparently 
it  usually  does  not  make  this  gas  as  abundantly  as 
does  B.  putrificus,  and  there  are  strains  which  do  not 
form  it  under  the  conditions  in  which  the  organism  has 
been  grown  on  blood  bouillon. 

Chronic  excessive  saccharo-butyric  intestinal  putre- 
faction is  a  widespread  condition  among  adults.  In 
children  it  is,  I  believe,  a  relatively  uncommon  occur- 
rence. Although  there  is  evidence  that  in  children 
some  acute  disturbances  of  short  duration  are  dependent 
upon  this  process,  as  people  grow  older  they  are  in 
general  more  subject  to  the  occurrence  of  this  type  of 
putrefactive  disorder.  The  grade  in  which  the  dis- 
turbance is  present  varies  within  wide  limits.  B. 
aerogenes  capsulatus  is  present  in  the  intestine  of  nearly 
all  adults,  and  there  are  probably  few  persons  who  from 
time  to  time  do  not  suffer  slight  temporary  derangements 
of  intestinal  digestion  connected  with  the  temporarily 
excessive  multiplication  of  these  anaerobes.  There  are 
probably  persons  who  during  an  entire  lifetime  have 
digestive  disturbances,  usually  slight  but  sometimes 
more  marked,  which  are  dependent  on  this  form  of 
putrefaction.  Under  such  circumstances  the  duration 
of  life  may  not  be  appreciably  shortened.  Persons  who 
have  long  had  disturbances  of  this  sort  may  attain  to 
seventy  or  seventy-five  years  of  age.  They,  however, 
suffer  in  various  ways  a  diminution  in  efficiency  and  are 
subject  to  various  obvious  disturbances.  It  sometimes 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      299 

happens  that  people  have  a  mild  grade  of  saccharo- 
butyric  putrefaction  for  a  long  period  of  time  without 
being  conscious  of  any  distinct  impairment  of  powers 
and  without  being  conscious  of  anything  approaching 
invalidism.  On  the  other  hand,  there  are  some  persons 
who  develop  this  type  of  putrefactive  disorder  in  a  high 
degree.  In  them  the  evidences  of  intestinal  indigestion 
are  pronounced,  and  there  is,  after  a  time,  a  decline  in 
the  capacity  of  the  organism  to  perform  work.  Such 
persons  develop  a  condition  of  distinct  invalidism,  and 
life  may  be  considerably  shortened  in  consequence  of 
the  intoxications  arising  from  this  condition.  As  a 
rule,  however,  the  severest  cases  of  chronic  saccharo- 
butyric  putrefaction  are  not  of  the  simple  type  at 
present  under  discussion,  but  are  rather  of  that  form 
which  is  associated  with  the  production  of  an  excess 
of  indol  in  the  intestinal  tract. 

Some  of  the  immediate  and  remote  consequences  of 
chronic  excessive  saccharo-butyric  intestinal  putrefac- 
tion may  be  briefly  enumerated.  As  already  stated, 
the  excessive  production  of  ammonium  butyrate  is 
apt  to  lead  to  irritability  of  the  digestive  tract,  and  this 
is  the  more  pronounced  if  there  is  also  an  abundant  indol 
production.  There  is  a  tendency  to  desquamation  of 
the  epithelium  of  the  digestive  tract  in  the  mouth  and 
stomach  and  probably  throughout  the  entire  digestive 
tract.  The  indications  of  this  desquamation  in  the 
mouth  and  on  the  tongue  are  often  plain.  A  frequent 
sign  of  such  desquamation  in  the  intestinal  tract  is 
the  presence  of  an  excessive  quantity  of  epithelium  or 


300      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

epithelial  nuclei  in  the  faeces.  The  patients  who  suffer 
from  this  condition  usually  do  not  tolerate  well  either 
carbohydrates  or  acids.  The  intolerance  of  carbohy- 
drates is  shown  by  the  occurrence  of  excessive  intestinal 
flatulence  and  sometimes  slight  diarrhoea  after  the  use 
of  considerable  meals  of  cereals  or  starchy  foods.  Sugars, 
especially,  are  apt  to  be  badly  borne.1  Probably  this 
intolerance  is  due  in  part  to  the  production  of  acids. 
There  are  cases  in  which  the  acid  production  from  sugar 
begins  very  rapidly  in  the  mouth,  and  a  certain  amount 
of  butyric  acid  may  be  formed  even  in  this  situation, 
owing  either  to  the  presence  of  B.  aerogenes  capsulatus 
in  the  mouth  or  to  the  presence  of  aerobic  butyric-acid 
producers.  Probably  the  tendency  to  diarrhoea  ob- 
served in  some  instances  is  due  to  the  irritative  action 
of  the  acids  formed  from  the  decomposition  of  the 
sugars  in  the  small  intestine.  This  intolerance  is 
naturally  most  marked  hi  those  persons  in  whom  evi- 
dences of  epithelial  desquamation  in  the  mouth  and 
elsewhere  are  most  pronounced.  The  mucous  mem- 
branes of  the  digestive  tract  are  almost  constantly  in  a 
state  of  excessive  irritation,  so  that  stimuli  which  in 
normal  people  would  meet  with  little  response  give 
rise  to  an  excessive  peristalsis  and  diarrhoea.  I  think 
it  not  improbable  that  in  advanced  cases  of  saccharo- 
butyric  putrefaction  B.  aerogenes  capsulatus  invades  the 


1  There  are  instances  in  which  excessive  indulgence  in  carbohy- 
drates is  followed  by  mental  depression  and  muscular  prostration. 
These  symptoms  appear  to  be  simply  a  great  exaggeration  of 
what  is  often  noticed  in  healthy  persons  after  similar  indulgences. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      301 

entire  extent  of  the  small  intestine  and  is  enabled  there 
to  decompose  sugar  with  the  formation  of  butyric  and 
other  acids.  Such  an  opportunity  to  grow  upon  a  car- 
bohydrate medium  might  lead  to  a  considerable  in- 
crease in  the  number  of  anaerobes.  These  on  passing 
into  the  large  intestine  would  find  an  opportunity  to 
set  up  their  putrefactive  activities  on  proteids  after 
the  carbohydrates  had  been  exhausted. 

The  consequences  of  chronic  excessive  saccharo- 
butyric  intestinal  putrefaction  are  by  no  means  limited 
to  disturbances  of  the  digestive  tract.  The  formation 
of  an  excessive  quantity  of  the  higher  fatty  acids  may 
be  presumed  to  lead  in  some  instances  to  the  absorp- 
tion of  an  excessive  quantity  of  these  acids.  As,  how- 
ever, the  organism  is  able  to  oxidize  the  fatty  acids 
with  great  readiness,  one  would  hardly  expect  that  so 
long  as  the  oxidizing  powers  of  the  organism  are  un- 
impaired there  would  be  any  evidence  of  an  increased 
excretion  of  organic  acids  in  consequence  of  this  ex- 
cessive absorption.  An  experiment  made  at  my  sug- 
gestion by  Dr.  A.  J.  Wakeman  bears  out  this  view.  A 
dog  weighing  about  eighteen  pounds  was  fed  on  a  fixed 
amount  of  meat,  namely  one  kilo  daily,  in  order  to 
study  the  influence  of  the  feeding  of  ammonium  buty- 
rate  upon  the  excretion  of  the  nitrogen  of  ammonia. 
During  the  preparatory  period  of  nine  days  determina- 
tions were  made  of  the  total  nitrogen  and  of  the  nitrogen 
of  ammonia  excreted  by  the  urine.  The  total  nitrogen 
of  ammonia  excreted  daily  amounted  to  between  one 
hundred  and  one  hundred  and  fifty-six  milligrams 


302      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

during  this  period  of  preparation.  During  the  five 
days  on  which  the  animal  received  daily  four  grams 
of  ammonium  butyrate  the  urine  collected  failed  to  show 
a  distinct  increase  in  the  nitrogen  of  ammonia  or  in  the 
proportion  between  the  nitrogen  of  ammonia  and  the 
total  nitrogen.  Thus  while  one  would  hardly  expect 
that  in  normal  organisms  on  a  moderate  diet  of  meat 
the  nitrogen  of  ammonia  would  be  appreciably  increased 
through  the  excessive  absorption  of  fatty  acids  which 
are  removed  as  compounds  of  ammonia,  it  is  nevertheless 
conceivable  that  in  conditions  of  disease  in  which  the 
oxidizing  powers  of  the  organism  are  as  a  whole  dimin- 
ished (or  taxed  to  the  utmost)  there  might  be  an  absorp- 
tion of  fatty  acids  in  such  excess  as  to  somewhat  increase 
the  output  of  the  nitrogen  of  ammonia.  In  other 
words,  there  would  then  be  a  slight  degree  of  acid  in- 
toxication or  acidosis  resulting  from  the  increased  ab- 
sorption of  the  volatile  fatty  acids.  There  are  individual 
instances  in  which  we  have  found  indications  from  the 
urine  that  this  is  probably  the  case,  but  the  evidence 
is  not  entirely  convincing.  The  subject  of  the  rela- 
tion between  excessive  saccharo-butyric  putrefaction 
and  the  excretion  of  an  increased  amount  of  nitrogen  of 
ammonia  calls  for  further  and  more  careful  observations, 
both  experimental  and  clinical. 

There  is  some  evidence  that  the  faecal  extracts 
obtained  from  persons  with  advanced  chronic  saccharo- 
butyric  putrefaction  may  exhibit  a  decided  hsemolytic 
action  on  the  red  blood  cells  of  rabbits  and  monkeys, 
and  in  some  instances  such  an  action  is  pronounced. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      303 

The  methods  that  have  been  employed  in  the  study 
of  the  haemolytic  action  of  the  faecal  extracts  in  such 
cases  are  not  wholly  beyond  criticism.  Nevertheless 
the  indications  seem  sufficiently  definite  that  there  are 
substances  formed  in  the  intestine  (in  extreme  cases  of 
excessive  saccharo-butyric  putrefaction)  that  are  capable 
of  haemolyzing  more  actively  than  is  the  case  with 
material  derived  from  healthy  persons  on  similar  diet. 
This  haemolytic  action  is  perhaps  in  part  referable  to 
ammonium  butyrate,  but  it  has  been  found  to  persist 
even  after  the  removal  of  the  ammonium  salts  of  the 
volatile  fatty  acids,  and  is  probably  due,  in  part  at  least, 
to  some  unknown  substance.  The  fact  already  mentioned 
in  speaking  of  the  characters  of  B.  aerogenes  capsulatus, 
that  this  organism  is  able  to  produce  haemolytic  sub- 
stances, is  worthy  of  notice  at  this  point,  since  in  many 
people  who  have  long  suffered  from  this  type  of  putre- 
faction there  are  distinct  evidences  of  anaemia.1  The 
onset  of  anaemia  in  excessive  saccharo-butyric  putre- 
faction is  usually  very  slow.  It  is  first  manifested  by 
indications  of  a  decreased  volume  of  blood  without  any 
decided  fall  in  the  percentage  of  haemoglobin  or  red  blood 
cells.  After  a  time,  however,  there  may  be  a  distinct 
fall  in  the  haemoglobin  and  later  in  the  red  blood  cells, 
so  that  a  moderate  or  considerable  grade  of  secondary 
anaemia  may  be  associated  with  the  intestinal  condition. 

1 1  have  discussed  at  some  length  the  relation  of  anaemia  to 
intestinal  infections  in  a  paper  entitled :  "  On  Bacterial  Processes 
in  the  Intestinal  Tract  in  Some  Cases  of  Advanced  Ansemia,  with 
Especial  Reference  to  Infection  with  B.  aerogenes  capsulatus  (B. 
Welchii),"  Journ.  of  Biol  Chem.,  ii,  p.  1,  1906. 


304      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

In  some  instances  which  I  have  observed  this  association 
has  been  apparently  a  very  close  one ;  that  is  to  say,  it 
has  appeared  as  if  the  anaemia  in  question  were  secon- 
dary to  the  chronic  intestinal  process,  since  other  causes 
of  anaemia,  such  as  malaria,  syphilis,  intestinal  worms 
or  parasites,  or  other  infections,  have  been  excluded 
with  a  very  high  degree  of  probability.  In  some  in- 
stances the  grade  of  anaemia  is  intense  and  the  patients 
may  present  the  blood  picture  and  clinical  characters 
of  a  progressive  pernicious  ansemia. 

The  occurrence  of  a  considerable  degree  of  ansemia 
in  any  case  of  advanced  saccharo-butyric  putrefaction 
must  depend  upon  an  excessive  destruction  of  red  blood 
cells  as  compared  with  the  reproduction  of  such  cells. 
Individuals  are  known  to  possess  very  different  powers 
of  regeneration,  and  it  is  doubtless  true  that  the  absorp- 
tion of  equal  quantities  of  hsemolytic  poison  by  two 
individuals  might  lead  to  very  different  results  so  far 
as  the  blood  is  concerned,  owing  to  differences  in  regen- 
erating power.  The  fact  that  a  patient  is  not  anaemic 
in  the  ordinary  sense,  that  is,  shows  no  reduction  below 
what  is  considered  a  normal  percentage  of  haemoglobin 
and  no  fall  in  the  number  of  red  blood  cells,  is  by  no  means 
a  positive  indication  that  there  is  not  an  excessive  blood 
destruction  going  on.  In  health  the  ability  to  regener- 
ate blood  cells  is  probably  much  in  excess  of  the  ordinary 
requirements.  This  margin  of  excess  may  not  be  ex- 
hausted for  some  years,  notwithstanding  a  considerably 
increased  drain  is  being  made  upon  the  regenerative 
structures  through  the  excessive  destruction  of  red  blood 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      305 

cells.  Sooner  or  later  a  definite  and  increasing  dispro- 
portion arises  between  the  destruction  and  reproduction 
of  red  blood  cells,  and  under  these  circumstances  there 
arises  a  slowly  or  more  rapidly  progressive  anaemia. 

In  some  instances  which  I  have  classed  as  falling  into 
the  category  of  the  simple  saccharo-butyric  type  of  putre- 
faction, depressive  mental  symptoms  have  been  noted. 
In  some  of  these  cases  an  abundant  growth  of  Gram- 
positive  diplococci  or  streptococci  have  been  found  in 
the  fermentation  tubes.  Whether  these  microorganisms 
have  any  part  in  the  production  of  neurotoxic  substances 
is  uncertain.  It  has  been  mentioned  that  B.  aerogenes 
capsulatus  is  said  to  make  poisons  capable  of  acting  on 
the  nervous  system,  but  the  bearing  of  this  fact  upon 
human  symptoms  is  still  obscure.  As  a  rule  well  marked 
nervous  symptoms  have  not  been  a  feature  in  the  class 
of  cases  to  which  the  term  saccharo-butyric  putrefaction 
has  been  applied. 

In  the  course  of  time,  in  well-marked  instances  of  the 
saccharo-butyric  type  of  excessive  chronic  intestinal 
putrefaction,  there  has  been  observed  a  considerable  loss 
in  weight  and  a  diminution  in  muscular  powers.  In 
spite  of  a  fairly  good  appetite  patients  are  unable  to  gain 
either  in  weight  or  in  strength.  Frequently  the  indica- 
tions of  premature  senility  are  evident.  This  is  notice- 
able in  an  atrophy  of  the  subcutaneous  fat  in  premature 
wrinkling  of  the  skin.  A  loss  of  general  vigor  is  apt  to 
be  associated  with  a  loss  in  sexual  power. 


306      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

III.  THE  COMBINED  INDOLIC  AND  SACCHARO-BUTYRIC 
TYPE  OF  CHRONIC  EXCESSIVE  INTESTINAL  PUTRE- 
FACTION 

The  association  of  the  features  of  the  two  types  of 
putrefactive  decomposition  already  described  is  common. 
In  cases  presenting  the  features  characteristic  of  both 
types  of  putrefactive  decomposition  the  two  processes 
often  vary  somewhat  independently.  It  is  in  a  measure 
an  arbitrary  matter  to  determine  what  cases  fall  under 
the  combined  type  and  what  cases  belong  under  the 
indolic  or  saccharo-butyric  type.  I  would  include  as 
falling  under  the  combined  type  of  putrefaction  all  cases 
in  which  putrefactive  anaerobes  of  the  intestine  are 
regularly  very  abundant  in  the  faeces  at  the  same  time 
that  there  is  a  persistent  indicanuria  of  high  grade  —  an 
indicanuria  not  immediately  and  markedly  influenced 
by  even  the  strictest  precautions  in  regard  to  the  dietary. 
In  the  combined  type  of  saccharo-butyric  putrefaction 
nervous  symptoms  are  apt  to  be  prominent  relatively 
early  in  the  course  of  the  affection.  These  symptoms 
are  excessive  emotional  irritability,  an  inclination  to 
mental  depression,  and  the  early  onset  of  muscular  and 
mental  fatigue.  At  a  somewhat  later  period  in  the 
course  of  pronounced  cases,  the  haemic  disturbances 
become  noticeable.  The  patients  grow  gradually  more 
and  more  anaemic.  There  may  be  periods  of  improve- 
ment, both  as  regards  the  anaemia  and  the  nervous 
symptoms,  but  on  the  whole  the  tendency  is  a  downward 
one,  and  from  year  to  year  the  patients  become  a  little 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      307 

less  robust  and  less  capable  of  rapid  recuperation  under 
favorable  hygienic  conditions.  After  a  time  —  com- 
monly, however,  not  until  the  process  has  been  a  very 
marked  one  for  ten  or  fifteen  years  —  the  patients  lose 
so  much  strength  as  to  be  unable  to  attend  to  ordi- 
nary business  occupations  without  very  great  effort.  A 
period  of  carefully  regulated  living,  free  from  anxieties, 
may  be  followed  by  a  considerable  degree  of  improve- 
ment, but  this  improvement  is  usually  extremely  slow. 
In  certain  cases  the  anaemia  ultimately  deepens,  and  the 
patient  may  present  the  picture  of  a  progressive  per- 
nicious anaemia.  In  other  instances  it  is  especially 
the  nervous  symptoms  which  increase,  and  periods  of 
depression  become  more  and  more  marked  and  of  longer 
duration.  The  mental  depression  may  become  so  pro- 
nounced as  to  necessitate  a  residence  of  the  patient  in 
a  sanitarium  or  asylum,  the  conditions  being  those  of 
mild  or  pronounced  melancholia.  As  already  mentioned 
when  discussing  the  character  of  the  toxic  effects  of  the 
various  poisons  absorbed  from  the  intestine,  it  is  highly 
probable  that  different  individuals  react  differently  to 
the  same  toxic  agencies.  If,  for  example,  there  be 
absorbed  from  the  intestine  substances  capable  of 
damaging  both  the  nervous  system  and  the  red  blood 
cells,  it  is  conceivable  (assuming  the  same  proportions 
and  amounts  of  these  substances  to  be  absorbed  in  each 
instance)  that  one  individual  would  become  invalided 
first  through  damage  to  the  nervous  system,  whereas 
the  invalidism  of  another  might  come  first  through  dam- 
age to  the  blood.  The  condition  of  invalidism  in  either 


308      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

case  would  lead  to  an  enforced  rest  and  perhaps  also  to 
improved  conditions  of  diet.  The  result  is  that  while 
the  improved  hygienic  conditions  may  not  lead  to  a 
restoration  of  normal  function,  there  is  for  a  time  a 
cessation  in  the  progress  of  the  injurious  action  of  the 
intestinal  poisons  upon  those  structures  that  are  most 
susceptible.  Even  in  cases  where  there  is  very  little 
or  no  improvement  in  respect  to  the  especially  suscep- 
tible tissues,  there  is  also  a  cessation  of  the  progressive 
damage  done  to  the  less  susceptible  cellular  elements. 
For  example,  a  patient  suffering  from  combined  indolic 
and  saccharo-butyric  excessive  intestinal  putrefaction 
may  succumb  on  the  side  of  the  nervous  system  and  be 
compelled  to  enter  an  asylum  on  account  of  mental 
depression.  Under  the  improved  hygienic  conditions 
there  may  be  only  a  little  improvement  in  the  nervous 
manifestations,  but  there  may  nevertheless  be  a  cessation 
of  the  slowly  progressive  loss  of  balance  between  the 
destruction  and  the  formation  of  red  blood  cells.  The 
patient  remains  moderately  ansemic,  but  does  not  grow 
extremely  so,  because  there  has  been  a  slight  mitigation 
of  the  absorption  of  substances  injurious  to  the  blood. 
It  is  in  fact  true  that  high  grades  of  anaemia  do  not 
develop  in  patients  who  suffer  from  the  combined  indolic 
and  saccharo-butyric  type  of  putrefaction  and  find  their 
way  into  an  asylum  on  account  of  nervous  symptoms. 

In  general,  one  may  say  of  the  combined  indolic  and 
saccharo-butyric  type  of  chronic  excessive  intestinal 
putrefaction  that  the  persons  in  whom  these  processes 
are  highly  developed  reach  a  state  of  chronic  invalidism 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      309 

more  rapidly  than  where  either  condition  is  alone  present. 
Not  only  do  the  nervous  symptoms  come  on  earlier,  but 
there  is  a  relatively  early  loss  in  weight  and  power. 
The  indications  of  premature  senility  maybe  pronounced. 
It  is  probable  that  atrophic  processes  are  not  limited 
to  the  fatty,  muscular,  and  blood  tissues.  It  seems 
probable  that  the  cells  of  the  liver  and  of  the  kidney 
undergo  premature  degenerative  atrophy  in  these  cases. 
This  is  doubtless  the  result  of  chronic  parenchymatous 
changes  due  to  constant  exposure  of  the  cells  to  cyto- 
lytic  toxic  agents  present  in  very  small  amounts  at  any 
one  time  but  acting  constantly.  We  are  still  far  from  a 
full  understanding  of  the  effects  of  enterogenic  poisons  on 
different  types  of  protoplasm.  One  tends,  for  example, 
to  assume  that  the  destruction  of  red  blood  cells,  in 
the  course  of  chronic  or  acute  infections  of  the  intestine 
with  the  gas-bacillus,  is  due  to  the  direct  hsemolytic 
action  of  hsemolyzing  agents  formed  in  the  intestine. 
It  is  possible,  nevertheless,  that  the  destruction  of  red 
cells  is  sometimes  accomplished  through  a  process  of 
phagocytosis  which  is  made  possible  by  injuries  to  red 
cells  inflicted  by  special  opsonins.1 

The  derangements  of  the  nervous  system  which  have 
been  mentioned  as  concomitants  of  the  combined  in- 
dolic  and  saccharo-butyric  form  of  excessive  intestinal 
putrefaction  —  mental  depression  and  muscle  fatigue  - 

1  Sir  A.  E.  Wright  tells  me  that  he  has  observed  pronounced 
phagocytosis  of  red  cells  in  a  case  of  pneumococcus  infection 
associated  with  a  pernicious  type  of  anaemia.  The  subject  of 
phagocytosis  of  red  cells  has  lately  been  investigated  by  Hektoen 
(Journ.  of  Infect.  Dis.,  iii,  p.  721,  1906). 


310      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

constitute  only  a  small  part  of  the  nervous  manifesta- 
tions of  this  pathological  process.  Almost  every  known 
expression  of  functional  disorder  of  the  nervous  system 
is  noted  in  some  of  the  subjects  of  this  variety  of  intestinal 
putrefaction.  But  it  would  confuse  rather  than  help 
us  to  make  a  list  of  these  derangements,  including  as 
they  do  almost  all  the  symptoms  encountered  in  the  pot- 
pourri of  neurasthenia .  If  we  could  distribute  these 
symptoms  with  confidence  into  those  that  are  clearly 
the  result  of  intestinal  intoxication  and  those  that  are 
due  to  derangements  of  circulation  or  other  mechanical  or 
dynamic  departures  from  normal  function,  it  would 
repay  us  to  attempt  their  classification.  At  present 
such  an  attempt  would  be  foolhardy  and  futile.  Only 
the  most  thoughtfully  and  carefully  conducted  clinical 
and  experimental  studies  can  help  us  to  determine  the 
influence  of  enterogenic  poisons  on  the  protoplasm  of 
nervous  structures,  and  the  opportunities  for  serious 
studies  of  this  kind  do  not  now  exist  anywhere  in  the 
world.  Among  the  problems  which  must  sooner  or  later 
be  approached  by  modern  methods  are  the  action  of 
enterogenic  poisons  on  the  motor  structures  of  the  central 
nervous  system,  on  the  sensory  paths  (both  peripheral 
and  central),  on  the  sympathetic  nervous  system,  and 
on  the  peripheral  and  central  mechanisms  that  subserve 
the  special  senses.  To  what  extent  these  various  struc- 
tures maybe  damaged  hi  consequence  of  chronic  excessive 
intestinal  putrefaction  is  uncertain.  There  are  instances 
of  typical  progressive  muscular  atrophy  (due  to  lesions 
of  the  ganglion  cells  of  the  anterior  horns)  in  which  there 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      311 

are  also  pronounced  evidences  of  excessive  intestinal 
putrefaction,  but  the  relationship  between  the  two 
series  of  phenomena  is  not  now  definable.  There  are 
cases  of  intestinal  putrefaction  in  which  B.  aerogenes 
capsulatus  is  the  prominent  microorganism  of  the  di- 
gestive tract  and  in  which  there  occurs  a  slow  muscular 
atrophy  associated  with  some  fibrillation  of  the  wasting 
muscle  bundles.  Possibly  in  such  instances  the  resistance 
of  the  motor  ganglion  cells  of  the  spinal  cord  is  distinctly 
below  that  of  normal  structures,  thus  rendering  these 
cells  especially  vulnerable  to  neurotoxic  substances 
made  in  the  digestive  tube.  There  are  also  cases  of 
multiple  neuritis,  resembling  alcoholic  neuritis,  in  which 
alcohol  can  have  no  etiological  part,  but  in  which  ante- 
cedent gastro-enteric  derangements  are  very  prominent. 
The  probability  that  these  instances  of  peripheral 
neuritis  (with  the  associated  psychosis)  are  in  reality 
due  to  intoxications  from  enterogenic  poisons  appears  to 
me  considerable,  although  the  data  now  at  my  command 
do  not  suffice  to  establish  this  view.  There  is  at  present 
no  evidence  that  infection  by  B.  aerogenes  capsulatus 
is  in  itself  capable  of  inducing  this  type  of  nervous 
disease. 

It  is  essential  to  realize  that  the  onset  of  severe  clinical 
manifestations  of  excessive  intestinal  putrefaction  may 
not  coincide  with  the  period  of  most  extreme  develop- 
ment of  the  gastro-enteric  process.  A  short  time  after 
therapeutical  measures  have  been  commenced  the  bac- 
terial conditions  in  the  tract  may  have  been  much 
mitigated.  It  may  thus,  be  unsafe  to  base  a  conclusion 


312      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

regarding  the  etiology  of  a  disease  upon  the  bacterial 
conditions  that  present  themselves  after  the  disease  has 
become  established.  I  observed  that  it  sometimes 
happens  in  the  course  of  a  pernicious  anaemia  that 
the  numbers  of  B.  aerogenes  capsulatus  in  the  faeces 
undergo  so  great  a  decrease  in  the  course  of  treatment 
that  the  microscopical  faecal  fields  present  a  nearly 
normal  appearance  with  respect  to  this  organism. 
Hence  the  failure  to  find  the  gas-bacillus  in  large  excess 
after  a  patient  has  for  some  weeks  or  months  had  the 
benefit  of  treatment  by  diet  and  rest  does  not  necessarily 
exclude  a  preceding  infection. 

I  believe  the  most  intense  period  of  the  saccharo- 
butyric  process  sometimes  precedes  the  development 
of  a  pernicious  anaemia  by  a  considerable  length  of  time. 
The  explanation  of  this  seemingly  paradoxical  view  lies 
in  the  fact  that  the  normal  defenses  of  the  organism 
must  be  greatly  impaired  before  a  pernicious  type  of 
anaemia  can  arise.  The  bacterial  process  involved  in 
breaking  down  these  defenses  (which  include  the  ability 
of  cells  to  bind,  oxidize,  and  pair  with  enterogenic 
poisons)  are  intensive  and  of  long  duration.  After  a 
time  there  develop  symptoms  of  weakness  which  make 
it  necessary  for  the  subject  of  the  gas-bacillus  infection 
to  live  with  much  greater  regard  for  hygienic  conditions; 
for  example,  with  more  rest,  more  out-of-door  life,  and 
a  more  restricted  dietary.  In  consequence  of  these 
changes  the  intensity  of  the  putrefactive  process  is 
mitigated.  The  quantity  of  injurious  products  absorbed, 
including  those  that  are  haemolytic,  may  become  so 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      313 

moderate  that  little  harm  could  be  accomplished  by  them 
in  a  person  with  normal  defenses.  But  in  a  person  with 
greatly  impaired  defenses  and  diminished  hsemopoi- 
etic  powers  (correlative  to  parenchymatous  changes 
in  the  hepatic  and  other  cells,  on  alteration  in  the  bone 
marrow)  the  absorbed  poisons  suffice  ultimately  to  make 
blood  destruction  preponderate  permanently  over  blood 
formation.  A  relatively  slight  putrefactive  process  in 
the  intestine  thus  ushers  in  the  signs  of  the  severe 
anaemia. 


METHODS  RELATING  TO  THE  MODIFICATION 
AND  CONTROL  OF  BACTERIAL  PROCESSES 
CONCERNED  IN  CHRONIC  EXCESSIVE  IN- 
TESTINAL PUTREFACTION 

THE  difficulty  of  formulating  measures  for  the  control 
of  the  bacterial  processes  concerned  with  the  occurrence 
of  chronic  excessive  intestinal  putrefaction  is  obvious. 
No  two  cases  that  come  under  observation  are  quite 
alike ;  hence  specific  measures  which  appear  appropriate 
in  one  case  cannot  be  recommended  without  modifica- 
tion in  another.  It  becomes,  therefore,  almost  impossi- 
ble to  describe  a  method  of  treatment  with  all  the 
detailed  modifications  that  are  necessary  in  order  to 
cover  adequately  the  specific  cases  with  which  one  has 
to  deal  in  practice.  Our  store  of  experience  is  as  yet  so 
incomplete  that  it  is  impossible  to  predict  in  many  instances 
the  outcome  of  the  measures  proposed.  This  is  equivalent 
to  the  admission  that  the  therapeutical  side  of  the  subject 
of  chronic  intestinal  putrefaction  is., still  ^in  a  largely 
experimental  stage.  It  will  require  many  years  of 
careful  observation  associated  with  a  large  amount  of 
experimental  work  to  enable  the  practitioner  to  place 
his  methods  of  treatment  on  a  really  scientific  basis. 
Nevertheless  there  are  certain  general  therapeutical 
guides  which,  though  by  no  means  adequate  for  the 
direction  of  the  practitioner  in  individual  cases,  are 

314 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      315 

helpful  in  forming  a  conception  'of  the  principles  that 
must  enter  into  the  treatment  of  chronic  infections  of 
the  digestive  tract  by  putrefactive  anaerobes.  It  must 
be  emphasized  that  the  degree  of  success  with  which 
these  general  principles  of  treatment  are  applied  in 
individual  instances  of  disease  will  depend  upon  an 
actual  knowledge  of  individual  peculiarities  pertaining  to 
patients. 

The  slighter  grades  of  chronic  excessive  intestinal 
putrefaction  are  as  a  rule  quickly  improved  by  suitable 
measures.  It  is  helpful  to  think  of  the  clinical  mani- 
festations in  these  cases  as  represented  graphically  by 
a  curved  line  running  at  a  variable  distance  below  a 
straight  horizontal  line  representing  the  separation  of 
physiological  from  pathological  manifestations.  A  line 
traced  above  this  critical  line  indicates  that  a  person 
has  no  symptoms  of  diminished  function ;  and  the  greater 
the  distance  between  the  two  lines,  the  greater  is  the 
reserve  or  margin  of  resisting  power  which  has  to  be  lost 
before  symptoms  of  derangement  set  in.  A  line  running 
below  the  critical  line  indicates  that  the  defensive  pro- 
cesses of  the  organism  are  no  longer  adequate  to  pre- 
vent clinical  manifestations  of  disease.  Where  derange- 
ments are  slight  it  may  be  assumed  that  there  will  be  a 
prompt  disappearance  of  symptoms  as  soon  as  there  has 
been  a  restoration  of  the  balance  between  the  powers  of 
resistance  and  the  agencies  underlying  disordered  func- 
tion. The  mere  disappearance  of  symptoms,  however, 
does  not  mean  that  a  condition  of  normal  health  has 
been  reestablished,  for  a  state  of  robust  health  would 


316      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

be  indicated  by  a  line  running  at  a  considerable  rather 
than  a  slight  distance  above  the  critical  line.  The 
mere  crossing  of  this  line  in  an  upward  direction 
connotes  the  disappearance  of  symptoms.  But  this 
does  not  necessarily  mean  health,  because  there  may  be 
a  margin  so  small  that  it  is  quickly  exhausted  by  a  detri- 
mental influence.  On  the  other  hand,  very  pronounced 
symptoms  may  exist  (especially  hi  cases  of  short  dura- 
tion) without  these  symptoms  necessarily  possessing  a 
grave  significance.  A  slight  improvement  in  physiologi- 
cal conditions  is  sufficient  to  make  the  line  indicative  of 
derangement  in  function  cross  the  critical  line  of  demar- 
cation between  physiological  and  pathological  conditions. 
This  conception  of  the  part  played  by  symptoms  as  an  indi- 
cation of  actual  states  of  functional  activity  is  helpful  in 
explaining  why  some  cases  are  so  much  more  refractory 
than  others.  In  long  standing  conditions,  in  which  a  high 
grade  of  intestinal  putrefaction  has  for  some  time  been 
present,  improvement  is  extremely  slow  even  under  the 
most  favorable  hygienic  conditions.  There  is  a  dis- 
couraging persistence  of  symptoms  until  the  critical  line 
is  reached.  The  depression  of  function  is,  however,  so 
considerable  that  there  may  be  a  real  gain  in  function 
without  an  immediate  and  corresponding  subjective  im- 
provement. In  such  cases  the  patient  seldom  accumu- 
lates an  adequate  functional  reserve  even  after  the 
disappearance  of  all  obtrusive  symptoms.  The  line 
representing  his  physiological  condition  must  be  traced 
close  above  the  critical  line,  and  a  slight  depression  in 
function  is  promptly  'followed  by  a  return  of  symptoms. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      317 

Thus  it  is  that  in  these  severe  types  of  intestinal  de- 
rangement relapses  are  common  and  discouragements 
frequent,  even  among  persons  who  from  time  to  time 
are  quite  free  from  definite  symptoms  of  disease. 

The  principles  entering  into  the  management  of  cases 
of  chronic  excessive  intestinal  putrefaction  may  be 
divided  into  three  groups.  First,  those  that  relate  to 
the  avoidance  of  putrefactive  bacterial  contamination  of 
the  food;  second,  those  that  relate  to  the  promotion 
of  prompt  digestion  in  and  absorption  from  the  small 
intestine;  third,  those  that  relate  to  agencies  designed 
to  reduce  the  numbers  of  putrefactive  anaerobes  living 
in  the  intestinal  tract.  It  seems  hardly  practicable  to 
separate  here  the  indolic  and  the  saccharo-butyric  types 
of  decomposition  from  the  standpoint  of  the  practical 
measures  to  be  employed  in  modifying  them,  especially 
as  the  subject  of  indolic  putrefaction  has  been  already 
considered  in  part. 

The  Avoidance  of  Putrefactive  Contamination  of  the 
Food.  —  As  regards  the  avoidance  of  bacterial  con- 
tamination of  the  food  with  injurious  organisms  it  is 
evident  that  care  in  regard  to  ordinary  principles  of 
cleanliness  must  be  of  importance.  In  a  large  propor- 
tion of  cases  of  chronic  excessive  intestinal  putrefaction 
the  hydrochloric  acid  of  the  gastric  juice  is  secreted  in 
diminished  amount  and  frequently  no  free  hydrochloric 
acid  can  be  detected  in  the  stomach.  Often  there 
is  also  a  moderate  degree  of  dilatation  of  the  stomach 
or  at  least  some  atony.  This  results  in  a  delay  in  the 
emptying  of  the  stomach,  which  in  the  absence  of  an 


318      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

adequate  secretion  of  hydrochloric  acid  is  favorable  to 
fermentative  decompositions  and  even  to  the  beginning 
of  putrefaction,  if  putrefactive  bacteria  are  abundantly 
present.  It  is  clear  that  in  such  cases  the  greater  the 
freedom  of  the  food  from  putrefactive  bacteria,  the  less 
will  be  the  liability  to  putrefaction  at  lower  levels,  since 
the  stomach  in  the  condition  under  consideration  is 
unable  to  extensively  destroy  such  bacteria,  even  in 
their  vegetative  forms.  In  the  present  connection  I 
lay  especial  stress  on  the  avoidance  of  putrefactive 
bacteria,  but  the  introduction  of  pathogenic  organisms 
related  to  the  colon  type,  including,  for  example,  organ- 
isms capable  of  inducing  dysentery,  should  also  be 
avoided,  since  any  injury  to  the  mucous  membrane  of  the 
tract  tends  to  impair  the  physiological  inhibitions  to  pu- 
trefactive decomposition.  The  use  of  cooked  food  goes  a 
long  way  toward  securing  conditions  of  sterility  within 
the  stomach.  It  is,  however,  usually  impracticable 
to  live  exclusively  on  food  that  is  sterile.  The  use  of 
milk,  for  example,  means  the  introduction  of  very  large 
numbers  of  bacteria.  So  long  as  these  bacteria  are 
lactic-acid  formers,  no  harm  is  done,  but  in  many 
samples  of  milk  there  are  putrefactive  organisms,  and 
these  may  be  present  in  large  numbers.  This  is  true 
of  B.  putrificus  and  of  an  organism  closely  resembling 
B.  aerogenes  capsulatus,  but  differing  ordinarily  from  it  in 
being  less  pathogenic  for  experimental  animals.  Cheese 
is  another  article  of  food  which  commonly  contains  large 
numbers  of  putrefactive  bacteria.  In  normal  stomachs 
these  putrefactive  bacteria  are  quickly  disposed  of ;  in 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      319 

cases  of  chronic  excessive  intestinal  putrefaction  the  gas- 
tric conditions  are  usually  such  as  to  make  the  stomach 
incapable  of  adequately  coping  with  the  putrefactive 
bacteria  introduced  with  the  cheese.  Cheese  is  there- 
fore an  article  which  should  generally  be  excluded  from 
the  dietary  of  nearly  all  cases  of  excessive  chronic 
intestinal  putrefaction,  although  some  forms  of  cheese 
(especially  those  which  are  newly  made  from  milk  con- 
taining few  putrefactive  bacteria)  may  be  permitted  in 
moderate  quantities.  In  eating  uncooked  fruit  it  is 
desirable  to  guard  against  the  organisms  found  on 
the  skin.  Fruits  therefore  should  be  always  peeled. 
Bacillus  putrificus  and  the  bacillus  of  malignant  oedema 
are  often  found  on  the  surface  of  fruits,  and  Dr.  Rettger 
has  found  the  latter  abundant  on  the  skin  of  bananas. 
The  question  of  the  sterilization  of  milk  may  be 
briefly  touched  upon  in  its  relation  to  the  dietary  of 
persons  suffering  from  chronic  excessive  putrefaction. 
So  far  as  the  treatment  of  chronic  putrefactive  disorders 
is  concerned,  I  think  it  preferable  to  avoid  sterilization 
except  where  the  milk  contains  considerable  numbers 
of  putrefactive  bacteria.  One  can  form  some  judgment 
of  this  point  by  permitting  samples  of  milk  to  stand 
in  fermentation  tubes  in  the  incubator  after  subject- 
ing them  to  a  single  partial  sterilization  by  the  process 
of  pasteurization.  Under  these  conditions  lactic-acid 
organisms  which  restrain  putrefactive  decomposition  are 
killed ;  the  surviving  spore-bearing  putrefactive  organ- 
isms of  the  gas-bacillus  type  reveal  their  presence  by 
setting  up  a  stormy  fermentation  of  the  milk.  Effective 


320      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

sterilization  involves  the  destruction  of  the  spores  of  the 
putrefactive  anaerobes  and  can  only  be  accomplished 
with  certainty  by  the  use  of  the  autoclave.  It  is  evi- 
dent from  what  has  been  just  said,  that  the  partial 
sterilization  of  milk  containing  putrefactive  organisms 
in  abundance  is  not  a  desirable  procedure,  since  it 
destroys  the  lactic-acid  bacteria  which  are  normally 
present  and  which  exert  an  antiputrefactive  action.  It 
is  safer  for  patients  to  drink  milk  containing  lactic-acid 
organisms  together  with  putrefactive  ones  than  to  drink 
the  latter  alone,  unless  these  are  very  few  in  number. 

An  important  measure  bearing  upon  the  introduction 
of  putrefactive  bacteria  into  the  intestine  is  the  proper 
cleansing  of  the  mouth.  Putrefactive  bacteria  such  as 
putrificus  are  not  uncommon  in  the  mouth,  especially 
where  there  is  dental  caries.  They  find  in  cavities 
sufficiently  anaerobic  conditions  for  their  development. 
Whether  other  forms  of  putrefactive  organisms  occur  in 
the  mouth  in  cases  of  chronic  excessive  putrefaction 
in  the  intestine  is  not  clear.  I  have  never  certainly 
found  B.  aerogenes  capsulatus.  The  growth  of  this 
organism  and  of  allied  strict  anaerobes  could  easily 
be  prevented  or  minimized  by  careful  cleansing  of  the 
teeth  and  especially  by  the  avoidance  of  the  lodging  of 
food  between  the  teeth.  The  maintenance  of  the  mouth 
in  a  relatively  cleanly  condition  through  the  intelligent 
and  free  use  of  the  toothbrush  and  through  the  employ- 
ment of  an  oxidizing  tooth  paste,  such  as  Pebeco,1 

^his  is  a  paste  containing  a  high  percentage  of  potassium 
chlorate. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      321 

is  a  material  aid  in  restricting  putrefactive  conditions  in 
the  upper  part  of  the  digestive  tract.  These  measures 
are  of  much  more  service  if  supplemented  by  the  process 
of  flossing  the  teeth.  It  is,  however,  easy  to  exaggerate 
the  importance  of  the  oral  conditions  especially  hi  the 
direction  of  assuming  that  a  really  cleanly  mouth  will 
insure  a  disappearance  of  excessive  putrefaction  in  the 
intestine.  While  it  is  evident  that  to  swallow  large 
numbers  of  putrefactive  anaerobes  which  have  grown 
in  the  mouth  (in  cases  where  the  stomach  is  unable  to 
destroy  these  organisms)  must  tend  to  increase  the 
intensity  of  the  putrefactive  processes  in  the  intestine, 
it  does  not  follow  that  a  patient  will  promptly  convalesce 
if  this  additional  increment  of  bacteria  be  removed. 
Some  improvement  is  perhaps  to  be  expected  through 
the  cleansing  of  a  very  offensive  mouth,  but  the  per- 
manent eradication  of  the  intestinal  conditions  (when 
this  is  possible)  depends  on  a  number  of  factors  and  not 
upon  one.  There  are  cases  in  which  an  oral  butyric 
putrefaction  occurs  very  rapidly  after  a  meal.  In  such 
cases  food  which  is  lodged  in  the  teeth  will  hi  the  course 
of  an  hour  develop  an  intense  odor  of  butyric  acid.  It 
is  not  yet  certain  upon  which  organisms  this  putrefaction 
depends.  It  is  not  impossible  that  the  decomposition 
may  be  due  to  aerobic  producers  of  butyric  acid,  but 
it  seems  probable  that  anaerobes  are  at  least  to  some 
extent  concerned  in  many  instances. 

The  suitable  care  of  the  stomach  may  also  be  a  factor 
in  controlling  putrefactive  decompositions  in  the  in- 
testines. In  persons  suffering  from  atony  of  the  stomach 


322      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

(with  or  without  pronounced  dilatation)  putrefactive 
microorganisms  may  gain  a  hold  and  initiate  high  up  in 
the  digestive  tract  a  process  which  normally  begins 
only  in  the  region  of  the  lower  ileum.  All  measures  that 
act  in  the  direction  of  stimulating  the  stomach  to  nor- 
mal motility  must  favor  the  mechanical  removal  of  the 
bacteria  concerned  in  putrefaction.  But  hygienic  meas- 
ures and  drugs  may  not  suffice  to  free  the  stomach  from 
putrefactive  organisms.  In  such  cases  the  practice  of 
lavage  may  be  very  helpful  and  may  give  quick  relief 
from  some  symptoms  of  intoxication,  especially  head- 
ache. Even  in  persons  in  whom  dilatation  is  not  marked 
the  use  of  lavage  before  breakfast  may  be  a  very  helpful 
measure,  and  the  selection  of  this  time  has  the  advantage 
of  not  depriving  the  patient  of  undigested  food. 

The  Promotion  of  Prompt  Digestion  and  Absorption  in 
the  Small  Intestine.  —  Generally  speaking  it  is  safe  to 
say  that  all  those  measures  which  aid  in  securing  prompt 
digestion  in  and  absorption  from  the  small  intestine  will 
operate  to  diminish  intestinal  putrefaction,  since  the 
outcome  of  prompt  absorption  in  the  region  of  the  small 
intestine  is  equivalent  to  offering  a  diminished  oppor- 
tunity for  the  attack  of  putrefactive  anaerobes  located 
in  the  ileum  and  large  intestine.  Probably  the  restora- 
tion of  normal  gastric  secretion  and  of  pancreatic  secre- 
tion is  the  most  important  physiological  agency  in 
securing  rapid  digestion  and  absorption  of  proteids 
from  the  small  intestine.  An  improvement  in  the 
quantity  of  gastric  juice  secreted  and  in  the  quantity 
of  the  hydrochloric  acid  which  it  contains  usually  goes 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      323 

hand  in  hand  with  the  betterment  of  motility.  The 
influence  of  imperfect  pancreatic  secretion  may  safely 
be  assumed  to  be  important,  but  in  this  case  direct 
clinical  observation  is  not  possible,  and  one  has  to  infer 
the  absence  or  presence  of  a  pancreatic  achylia  from  the 
manner  in  which  the  proteid  food  in  a  test  meal  is  at- 
tacked by  the  digestive  juices.  The  use  of  small  cheese- 
cloth bags  containing  meat  in  a  state  of  moderate  sub- 
division may  be  helpful  in  measuring  the  ability  of  the 
intestinal  enzymes  to  carry  on  the  digestion  of  meat 
proteids.1  The  use  of  this  method  as  an  index  of  pan- 
creatic digestion  can  hardly  be  regarded  as  free  from 
error. 

The  most  important  physiological  factor  in  the  partial 
or  complete  restoration  of  pancreatic  secretion  is  prob- 
ably rest.  The  influence  of  fatigue  upon  the  digestive 
processes  is  often  very  clearly  demonstrated  in  a  given 
individual,  and  the  removal  of  opportunity  for  fatigue 
is  conversely  a  factor  in  determining  recovery.  The 
rest  which  should  be  secured  in  such  cases  is  in  part 
physical,  in  part  mental  and  emotional  and  sexual. 
Many  patients  commit  the  error  of  exercising  freely  when 
rest  is  far  more  important.  The  effect  of  mental,  emo- 
tional, and  sexual  fatigue  upon  the  digestive  tract  has 
not  been  so  carefully  studied  as  it  deserves,  but  there  is 
on  doubt  that  in  each  case  the  expenditure  of  nervous 
energy  may  lead  to  very  similar  results  as  regards  the 
digestive  organs.  Rest  from  work  of  a  taxing  character 
may  be  an  extremely  important  factor  in  the  restoration 

1  This  procedure  was  lately  suggested  by  A.  Schmidt. 


324      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

of  normal  gastro-enteric  secretions.  In  many  persons 
emotional  fatigue,  such  as  often  results  from  strenuous 
business  activity  or  from  some  kinds  of  recreation,  has  a 
distinctly  harmful  influence.  Even  the  interest  attend- 
ant on  free  and  animated  conversation  may  be  in- 
jurious. In  the  case  of  fatigue  of  sexual  origin  great 
individual  differences  in  susceptibility  are  manifested 
by  different  persons.  In  all  cases  of  long-standing 
chronic  putrefactive  disorder  in  the  intestine  it  becomes 
important  to  take  cognizance  of  any  sexual  factor  that 
may  lead  to  fatigue.  This  relationship  is  one  of  the 
utmost  importance  and  is  frequently  overlooked  by 
physicians  in  their  regulation  of  the  lives  of  patients 
suffering  from  chronic  digestive  disorders.  It  is  a 
very  important  point  in  this  connection  to  realize  that  an 
intelligent  abstinence  from  sexual  excitement  should  be 
practiced  before  such  abstinence  is  forced  by  the  onset 
of  impotence.  When  this  has  occurred,  the  conditions 
are  probably  much  less  favorable  for  the  restoration  of 
normal  secretory  activity  in  the  stomach  and  intestine. 
It  is  customary  in  cases  where  the  free  hydrochloric 
acid  of  the  gastric  juice  is  regularly  diminished  to  ad- 
vise the  use  of  hydrochloric  acid  after  meals  in  order  to 
compensate  the  diminished  secretion  of  the  acid.1  In 
some  instances  the  use  of  hydrochloric  acid  is  distinctly 

1  The  absence  of  free  hydrochloric  acid  in  the  gastric  juice  is 
a  feature  of  nearly  all  cases  of  advanced  saccharo-butyric  putre- 
faction. The  influence  of  gastric  secretion  has  recently  been  studied 
and  discussed  by  D.  van  Tabora  in  its  relation  to  intestinal  pu- 
trefaction. "Ueber  die  Beziehungen  zwischen  Magensaftsecretion 
und  Darmfaulniss,"  Deutsche  Archiv  f.  klin.  Med.,  Ixxxvii,  p.  254, 
1906. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      325 

beneficial  if  one  may  judge  by  the  feelings  of  the  patient 
and  by  the  diminution  in  the  excretion  of  indican  which 
is  noted.  Among  the  long-standing  cases  of  chronic 
excessive  intestinal  putrefaction,  especially  in  cases  of 
the  combined  indolic  and  saccharo-butyric  type,  the  use 
of  hydrochloric  acid  is  often  attended  by  little  improve- 
ment. The  stomach,  indeed,  often  irritable  or  unduly 
sensitive,  may  not  accept  even  moderate  quantities  of 
the  acid  without  showing  indications  of  slight  gastritis 
or  local  discomfort.  The  use  of  digestive  enzymes  such 
as  pepsin,  trypsin,  pancreatin,  etc.,  has  been  much  lauded. 
It  is  possible  that  they  do  good  in  some  instances,  but 
I  have  never  been  convinced  that  their  use  is  really  an 
important  factor  in  determining  the  ultimate  outcome 
in  marked  cases  of  chronic  excessive  intestinal  putrefac- 
tion. The  use  of  an  efficient  diastatic  ferment  gives,  I 
think,  more  tangible  results,  and  there  are  cases  in  which 
a  better  utilization  of  carbohydrates  is  noticeable  in  con- 
sequence of  the  use  of  an  active  diastase.  The  criterion 
in  such  cases  has  been  the  better  tolerance  for  carbohy- 
drates which  is  manifested  by  the  reduction  in  habitual 
flatulence,  especially  in  the  upper  part  of  the  digestive 
tract.  I  know  of  no  observations  claiming  to  demon- 
strate a  direct  influence  either  of  diastatic  or  proteoclastic 
ferments  upon  the  excretion  of  the  ethereal  sulphates  or 
indican  or  upon  the  numbers  of  putrefactive  bacteria 
in  the  large  intestine. 

Careful  mastication  of  the  food  is  certainly  an  important 
factor  in  determining  how  it  shall  be  utilized.  But  one 
may  readily  exaggerate  the  influence  of  this  factor,  and 


326      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

this  has,  I  think,  been  done  in  some  recent  researches. 
There  is,  however,  no  doubt  that  in  cases  where  there  is 
a  failure  of  the  stomach  to  secrete  free  hydrocholric  acid 
the  careful  prolonged  mastication  of  the  food  much 
diminishes  the  opportunity  for  stagnation  in  the  stomach, 
while  it  subsequently  makes  it  less  likely  that  undi- 
gested proteid  will  appear  in  the  large  intestine  to  be 
attacked  there  by  putrefactive  anaerobes.  The  fine 
subdivision  of  the  food  before  it  is  eaten  is  often  very 
helpful,  especially  in  persons  whose  teeth  do  not  permit 
full  mastication.  I  question,  however,  whether  the  com- 
minution of  meat  outside  the  body  is  a  real  substitute 
for  its  equally  fine  subdivision  through  the  mastication 
by  the  patient,  since  in  the  latter  case  there  is  the  ad- 
vantage of  an  ultimate  admixture  with  the  enzymes 
of  the  saliva.  In  most  cases  benefit  is  derived  both 
from  a  fine  subdivision  of  meats  outside  of  the  body 
and  from  their  further  subdivision  through  prolonged 
mastication.  The  tolerance  for  meats  as  measured  by 
clinical  phenomena  is  often  greatly  increased  by  insisting 
that  the  patient  give  due  attention  to  mastication. 

The  avoidance  of  chemical  and  mechanical  irritants 
assumes  much  importance  in  some  instances  of  chronic 
excessive  intestinal  putrefaction.  Among  the  chemical 
irritants  may  be  mentioned  the  use  of  condiments  such 
as  pepper  and  mustard,  and  the  use  of  free  acids  such  as 
vinegar  and  lemon  juice,  and  indulgence  in  an  excess  of 
salt,  this  being  an  error  often  committed  by  neurasthenic 
patients  suffering  from  putrefactive  disorders.  The  ex- 
cessive use  of  salt  is  stated  by  some  investigators  to  be 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      327 

operative  in  bringing  about  the  removal  of  too  much 
alkali  from  the  body,  thus  favoring  a  degree  of  acidosis. 
Among  mechanical  factors  one  has  to  consider  mainly 
the  consistence  of  food.  The  use  of  raw  apples,  of  un- 
cooked celery,  and  of  spinach,  and  the  use  of  salads  may 
be  detrimental  for  purely  mechanical  reasons.  Some- 
times the  detrimental  effect  shows  itself  in  the  produc- 
tion of  colic,  in  other  cases  it  is  manifested  by  an  undue  re- 
tention of  the  food  within  the  stomach,  where  it  excites 
discomfort.  It  has  been  already  stated  that  there  are 
long-standing  cases  of  excessive  intestinal  putrefaction 
in  which  there  is  evidence  of  an  abnormal  sensitiveness 
of  the  partially  denuded  mucous  membrane.  In  cases 
where  the  stomach  is  sensitive  even  to  the  presence  of 
moderate  quantities  of  food  that  has  been  carefully 
masticated,  it  is  desirable  to  use  a  demulcent  (such  as 
flaxseed  tea)  before  meals.  This  is  often  a  highly  effi- 
cient measure  in  allaying  gastric  tenderness.  It  may  be 
desirable  to  give  a  demulcent  drink  before  each  meal 
during  a  long  period  of  time. 

It  is  obvious  that  in  order  to  secure  the  best  possible 
conditions  of  resorption  from  the  small  intestine  it  is 
important  not  to  permit  the  consumption  of  excessive 
quantities  of  food.  This  is  especially  important  in  the 
case  of  proteids,  particularly  those  of  meat  and  milk. 
The  use  of  an  excessive  quantity  of  meat  frequently 
goes  hand  in  hand  with  imperfect  mastication.  The 
result  is  that  many  masses  of  muscle  fiber  find  their  way 
through  the  small  intestine  into  the  lower  ileum  and 
large  intestine,  where  they  are  attacked  by  putrefac- 


328      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

tive  bacteria.    The  putrefactive  bacteria  find  in  meat 
proteid  and  casein  good  media  for  their  support. 

The  occurrence  of  large  numbers  of  fragments  of  meat 
or  smaller  aggregations  of  meat  fibers  in  the  fa3ces  is 
an  indication  of  the  imperfect  utilization  of  meat  and 
should  operate  as  a  signal  for  its  more  cautious  and 
intelligent  use.  It  has  already  been  mentioned  that 
the  intestinal  contents  of  carnivora  contain  many  more 
putrefactive,  spore-bearing  bacteria  than  is  the  case 
with  the  herbivora.  The  full  meaning  of  this  observa- 
tion is  not  at  the  present  time  clear.  As  certain  an- 
aerobes, especially  the  gas-bacilli,  are  closely  associated 
with  the  development  of  some  putrefactive  disturbances 
of  high  intensity,  it  seems  worth  while  to  investigate 
more  carefully  than  has  yet  been  done  the  influence  of 
meat  upon  the  growth  of  the  putrefactive  anaerobes. 
Until  further  knowledge  has  been  obtained  in  regard  to 
the  influence  of  meat  upon  the  development  of  putre- 
factive anaerobes,  in  cases  of  well-marked  saccharo- 
butyric  putrefaction,  it  seems  rational  to  advise  the 
practice  of  moderation  in  the  use  of  meats  in  the  dietary 
of  such  patients.  In  practice  I  restrict  the  use  of  meat 
to  one  meal  each  day  and  keep  its  amount  moderate. 
There  may  even  be  conditions  in  which  there  is  something 
to  be  gained  by  eliminating  meat  entirely  from  the  die- 
tary for  short  periods  of  time.  The  desirability  of  this 
more  extreme  measure  must  be  judged  partly  by  the 
clinical  effects.  It  may  be  found  that  in  some  persons 
who  have  long  been  accustomed  to  the  use  of  large 
quantities  of  meat  in  the  dietary,  a  complete  deprivation 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      329 

would  be  followed  by  loss  of  strength,  and  this  would 
hardly  be  compensated  for  by  a  slight  gain  in  the  direc- 
tion of  a  diminution  of  the  anaerobes  in  the  large 
intestine. 

It  is  often  a  difficult  matter  to  determine  how  much 
food  it  is  safe  to  permit  a  patient  with  chronic  excessive 
saccharo-butyric  putrefaction.  If  the  patient  be  weak, 
anaemic,  and  emaciated,  or  muscularly  atrophic,  there 
is  often  a  strong  temptation  to  feed  generously  or  indeed 
excessively.  I  consider  it  bad  practice  to  urge  the  use 
of  large  amounts  of  food  at  the  beginning  of  a  course  of 
treatment,  since  this  must  result  in  at  least  some  exag- 
geration of  the  putrefactive  process.  But  if  rest  can  be 
secured  to  the  patient  and  a  more  thorough  digestion 
and  resorption  of  food  can  be  achieved,  it  becomes  safe 
to  increase  the  food  gradually.  It  is  much  better  to 
devote  a  few  weeks  to  this  elevation  of  the  digestive 
functions  than  to  proceed  hastily  to  inaugurate  a  gener- 
ous regimen.  Even  under  the  most  favorable  conditions 
the  effect  of  the  diet  must  be  carefully  watched.  A  dis- 
tinct increase  in  the  ethereal  sulphates,  an  increase  in 
the  numbers  of  gas-bacilli  in  the  movements,  an  increase 
of  intestinal  flatulence  or  the  development  of  emotional 
irritability  or  mental  depression  are  signs  that  the  food 
should  be  decreased  in  quantity.  Intestinal  flatulence 
calls  for  a  diminution  in  carbohydrate  food. 

Methods  designed  to  reduce  the  Numbers  of  Putre- 
factive Anaerobes.  —  Among  the  agents  most  used  with 
a  view  to  reducing  fermentative  and  putrefactive  de- 
composition in  the  gastro-enteric  tract  are  the  so-called 


330      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

intestinal  antiseptics.  A  considerable  literature  exists 
in  regard  to  them.  Opinion  as  to  their  efficacy  is  di- 
vergent. I  shall  not  undertake  to  discuss  here  the 
literature  bearing  on  the  subject,  for  probably  all  of  the 
experiments  that  have  been  conducted  with  a  view  to 
determining  the  value  of  intestinal  antiseptics  have 
left  out  of  account  a  quantitative  study  of  the  putre- 
factive anaerobes  of  the  f seces  —  a  study  which  obviously 
is  beset  with  great  difficulties,  and  could  only  be  under- 
taken under  especially  advantageous  conditions  for 
work.1  In  some  of  the  experiments  upon  this  subject 
observations  have  been  made  on  the  excretion  of  the 
ethereal  sulphates,  the  indican,  and  the  phenolic  bodies 
of  the  urine.  These  unquestionably  possess  a  certain 
value,  and  if  the  observations  be  sufficiently  long  con- 
tinued and  properly  controlled,  may  be  regarded  as 
conclusive  indications  as  to  the  intensity  of  putrefaction. 
One  difficulty  in  measuring  the  action  of  many  of  the 
antiseptic  substances  which  have  been  used  depends 
on  the  fact  that  they  either  decompose  with  the  libera- 
tion of  aromatic  substances  capable  of  pairing  with 
sulphuric  acid  and  forming  ethereal  sulphates,  or  they 
themselves  are  aromatic  bodies  capable  of  pairing  in  this 
manner.  A  study  of  the  indican  is  not  open  to  this 
objection,  but  as  already  pointed  out  there  are  cases  of 
intestinal  decomposition  in  which  the  ethereal  sulphates 
may  be  considerably  above  the  normal,  although  little 
or  no  indican  is  excreted.  Again,  in  such  observations 

1  Much  of  the  modern  literature  relative  to  this  subject  is  given 
by  von  Tabora,  loc.  cit. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      331 

it  is  most  important  that  the  quantity  of  proteid  food 
(especially  of  meat)  should  be  regulated  in  an  exact 
manner,  since  an  increase  of  putrefaction  in  the  intestine 
through  the  use  of  excessive  quantities  of  meat  can  easily 
be  demonstrated. 

I  have  made  some  observations  on  the  action  of  so- 
called  intestinal  antiseptics,  and  I  have  reached  the  con- 
clusion that  most  of  them  do  very  little  good  in  effecting 
a  dkninution  of  the  putrefactive  anaerobes  of  the  in- 
testine. Their  ability  to  control  fermentative  processes 
in  the  stomach  cannot,  I  think,  be  questioned,  and  in 
cases  where  such  processes  are  excessive  they  may 
indirectly  do  good  by  diminishing  the  opportunities  for 
putrefaction  in  the  intestine  by  placing  obstacles  in  the 
way  of  the  development  of  the  sugar-splitting  gas-form- 
ing anaerobes.  It  cannot  be  denied  that  through  the 
use  of  glutoid  or  other  protective  capsules  antiseptics 
can  be  made  to  reach  the  intestine  itself  before  they  are 
liberated.  The  tendency  of  such  antiseptics  when  used 
in  practical  doses  to  enter  into  combination  with  many 
substances  outside  the  bodies  of  the  living  bacteria 
must  be  regarded  as  greatly  diminishing  their  ideal 
efficiency,  estimated  on  the  supposition  that  they  act 
simply  to  kill  or  arrest  the  growth  of  living  microorgan- 
isms. I  have  found  in  certain  instances  that  salicylates, 
aspirin,  and  salol  have  exerted  some  action  in  diminish- 
ing the  output  of  indican,  but  beyond  this  I  have  not 
been  able  to  satisfy  myself  that  the  effect  of  intestinal 
antiseptics  is  pronounced.  In  many  cases  they  are  not 
well  tolerated  by  the  stomach  after  they  have  been  used 


332      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

for  a  time,  and  may  thus  do  harm  to  the  structures  on 
which  normal  secretion  depends.  I  do  not  feel  that  the 
subject  of  intestinal  antisepsis  has  been  developed  in  a 
scientific  manner,  and  very  carefully  planned  experi- 
ments may  yet  teach  us  that  certain  substances  possess 
considerable  value  when  used  under  appropriate  con- 
ditions. At  present  antiseptics  are  used  in  an  empirical 
and  usually  unintelligent  way.  It  seems  to  me  on  theo- 
retical grounds  that  agents  which  exert  an  oxidizing 
action  in  the  large  intestine  are  among  those  worthy  of 
careful  study.  Some  of  the  oxides  of  manganese  liberate 
their  oxygen  slowly  and  would  appear  on  this  account 
to  be  suitable  for  studies  of  this  kind.  There  is,  indeed, 
some  evidence  that  the  dioxide  of  manganese  may  act 
beneficially  upon  putrefactive  processes  in  the  large 
intestine,  but  a  scientific  demonstration  of  the  fact  is, 
I  believe,  lacking. 

Experiments  made  by  Dr.  Wakeman  at  my  suggestion 
in  reference  to  the  action  of  oxidizing  substances  upon 
the  contents  of  the  large  intestine  did  not  give  results 
encouraging  to  the  view  that  such  agents  are  likely  to 
be  in  a  high  degree  efficient  in  mitigating  the  activities 
of  putrefactive  anaerobes.  He  experimented  with  dogs 
showing  a  high  degree  of  indicanuria  and  injected  into 
the  large  intestine  at  various  points  a  solution  of  hydro- 
gen peroxide.  In  other  experiments  ferric  sulphate 
was  used  as  a  catalyzer  in  recognition  of  the  fact  that 
the  presence  of  this  salt  in  small  quantities  renders  cer- 
tain oxidations  of  organic  material  much  more  efficient. 
Different  percentages,  ranging  from  one-half  of  one  per 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      333 

cent,  to  about  two  per  cent,  of  hydrogen  peroxide,  were 
employed  in  different  experiments.  The  solution  of 
hydrogen  peroxide  was  slowly  introduced  and  in  large 
volume,  half  a  liter  or  more  being  injected  in  the  course 
of  an  experiment  extending  over  many  hours.  In  these 
experiments  no  distinct  decline  in  the  indican  was 
observed.  It  is  possible,  of  course,  that  different  re- 
sults may  be  obtainable  with  other  oxidizing  agents  or 
with  oxidizing  agents  brought  into  the  intestine  in  a 
different  way.  The  results  might  have  been  more  con- 
clusive had  the  peroxide  been  introduced  into  the  ileum. 
It  is  well  known  to  clinicians  that  the  use  of  laxatives 
is  followed  by  great  temporary  benefit  in  many  cases 
of  excessive  intestinal  putrefaction  associated  with  con- 
stipation, sometimes  even  if  this  is  not  pronounced.  Some 
advise  the  use  of  salts,  others  of  cascara  preparations, 
and  still  others  are  partial  to  the  employment  of  calomel. 
That  there  is  an  actual  reduction  in  the  excretion  of 
ethereal  sulphates  and  of  various  individual  products  of 
putrefaction  after  the  use  of  a  laxative  is  certain.  The 
explanation  is  of  course  very  simple.  The  reduc- 
tion depends  on  diminished  absorption  from  the  intesti- 
nal tract  owing  to  the  acceleration  of  the  contents  of 
the  digestive  tract.  A  similar  phenomenon  is  witnessed 
in  cases  of  even  severe  diabetes  in  which  the  sugar  may 
drop  very  much  during  the  period  of  action  of  a  dose  of 
calomel,  or  some  other  cathartic.  Notwithstanding  the 
immediate  benefit  to  be  obtained  from  cathartics  I  be- 
lieve they  must  be  employed  with  much  discrimination 
and  caution.  It  is  easy  to  render  the  digestive  tract 


334      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

excessively  irritable  through  their  use,  and  it  often  hap- 
pens that  patients  fail  in  nutrition  owing  to  the  diminished 
absorption  of  foodstuffs.  The  long-continued  and  fre- 
quent use  of  cathartic  remedies  has  in  my  experience 
nearly  always  resulted  badly.  I  think  laxatives  should 
be  employed  mainly  for  the  control  of  the  disturbances 
of  a  subacute  or  acute  character  arising  hi  the  course  of 
chronic  derangements  rather  than  for  the  treatment  of 
the  chronic  conditions  themselves.  If  it  is  possible  to 
use  food  containing  an  abundance  of  cellulose,  this  may 
have  a  beneficial  effect  in  the  direction  of  preventing 
constipation,  but  it  frequently  happens  that  patients 
who  suffer  from  constipation  are  also  excessively  sensi- 
tive to  those  foods  containing  much  cellulose  and  show 
gastric  disturbances  from  their  use. 

The  idea  that  pathological  bacterial  processes  in  the 
intestinal  tract  may  be  favorably  modified  in  a  clinical 
sense  by  making  use  of  the  antagonistic  properties  of 
certain  harmless  microorganisms  is  by  no  means  a  new 
one.  It  has  long  seemed  probable  that  the  well-known 
beneficial  action  of  fermented  milks  such  as  Kefir  and 
Kumyss  is  in  part  due  to  the  restraining  action  exerted 
by  microorganisms  contained  in  these  drinks  upon  the 
harmful  bacteria  in  the  digestive  tract.  The  action  has 
been  attributed  in  these  cases  largely  to  the  lactic-acid- 
forming  bacteria  concerned  in  the  fermentation.  The 
fermented  milk  known  as  Matzoon  is  a  similar  preparation. 
Lately  there  has  been  placed  on  the  market  a  fermented 
milk  which  has  been  named  Badllac.  The  chief  or- 
ganism in  this  fermented  milk  is  a  lactic-acid  producer 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      335 

which  has  been  studied  by  Professor  Metchnikoff.1  It  is 
capable  of  inducing  a  high  grade  of  acidity  in  milk,  but 
does  not  grow  readily  on  other  media.  This  lactic- 
acid  producer  is  said  by  Professor  Metchnikoff  to  be 
entirely  harmless  and  has  been  used  by  him  and  his  as- 
sociates as  a  means  of  lowering  the  putrefactive  processes 
in  the  digestive  tract.  One  feature  of  superiority  claimed 
for  Bacillac  is  that  it  does  not  contain  any  yeasts.  This 
is  a  point  of  some  importance,  since  it  is  probable  that 
some  of  the  fermented  milks  do  contain  yeasts  capable 
of  exerting  a  detrimental  action  on  the  human  organism. 
Whether  the  Bacillac  preparation  will  show  itself  to  be 
superior  in  a  therapeutic  way  to  other  fermented  milks 
from  which  undesirable  yeasts  have  been  excluded 
must  be  regarded  as  an  open  question  and  one  that  can 
be  decided  only  by  extensive  and  very  careful  ex- 
perimentation. There  is  certainly  much  to  recom- 
mend the  view  that  putrefactive  intestinal  processes 
are  favorably  influenced  in  their  clinical  course  by 
fermented  milk  containing  an  abundance  of  lactic 
acid  and  lactic-acid  organisms.  The  subject  is  one, 
however,  which  is  very  far  from  resting  on  a  scientific 
basis,  and  a  large  amount  of  most  careful  research  is 
necessary  to  establish  the  exact  position  of  this  prin- 

1  Dr.  Collins  found  the  organism  to  be  Gram-positive,  similar 
to  B.  aerogenes  capsulatus  in  morphology,  but  larger  and  incapable 
of  making  indol  or  hydrogen  sulphide.  The  presence  and  growth 
of  this  organism  in  milk  flasks  inoculated  with  human  faeces  con- 
taining an  excessive  number  of  gas-bacilli  appeared  to  exert  a 
restraining  effect  on  putrefaction.  The  maintenance  of  an  acid 
reaction  is  essential  to  this  restraint. 


336      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

ciple  of  treatment.  It  is  important  to  determine  the 
influence  exerted  by  the  lactic-acid  bacteria  themselves. 
It  is  by  no  means  certain  that  most  of  the  beneficial 
influence  exerted  by  the  fermented  milks  is  not  depend- 
ent on  the  lactic  acid  existing  preformed  in  the  milk. 
Whether  the  lactic-acid  bacilli  in  a  thoroughly  fer- 
mented milk  go  on  producing  lactic  acid  in  the  digestive 
tract  is  uncertain  and  probably  depends  on  the  presence 
or  absence  of  fermentable  carbohydrates.  If  it  can  be 
shown  that  any  type  of  lactic-acid  bacilli  is  capable  of 
carrying  on  its  activities  in  the  ileum  and  large  intestine 
under  anaerobic  conditions,  with  a  restraining  action 
upon  anaerobic  putrefactive  spore  bearers  (such  as  B. 
aerogenes  capsulatus),  an  important  contribution  will 
have  been  made  to  rational  therapeutics.1 

Another  therapeutic  method  which  has  been  syste- 
matically employed  in  recent  years  in  many  cases  of 
intestinal  disease  is  irrigation  of  the  colon.  It  is  even 
possible  to  introduce  a  tube  through  the  sigmoid  flexure 
into  the  descending  colon,  and  in  some  instances  the 
tube  may  be  passed  still  further  in  the  direction  of  the 
ileocaecal  valve.  By  means  of  physiological  salt  solu- 
tionTne  large  intestine  has  in  many  cases  been  washed 
free  of  its  contents.  This  procedure  has  now  been 
frequently  practiced  with  extremely  beneficial  results 
in  the  direction  of  diminishing  excessive  intestinal  pu- 
trefaction. I  have  known  it  in  several  instances  to  be 
followed  by  a  reduction  in  the  output  of  ethereal 

1  The  bacillus  of  Bacillac  grows  well  in  milk  under  anaerobic 
conditions. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      337 

sulphates  and  in  the  excretion  of  indican  by  the  urine. 
Coincidentally  there  has  been  definite  relief  from  pro- 
nounced symptoms  such  as  headache,  mental  depression, 
irritability,  intestinal  flatulence,  etc.  In  several  instances 
of  advanced  ansemia  (including  some  showing  the  blood 
changes  of  the  pernicious  form)  there  has  been  a  very 
rapid  improvement  in  the  haemoglobin  and  red  blood 
cells,  together  with  a  prompt  disappearance  of  megalo- 
blastic  and  other  pathological  forms  of  red  blood  cells. 
There  is  no  room  for  doubt  that  the  intelligent  practice 
of  high  intestinal  lavage  leads  to  considerable  improve- 
ment in  many  cases  of  chronic  saccharo-butyric  putre- 
faction. The  beneficial  effects  have  been  pronounced 
and  prompt  in  some  cases  where  an  extreme  indolic 
putrefaction  was  associated  with  the  saccharo-butyric 
type.  If  the  lavage  be  practiced  cautiously  with  respect 
to  the  avoidance  of  an  excessive  volume  of  fluid,  the 
method  may  be  applied  for  a  considerable  period  of  time 
without  discernible  harmful  effects.  It  is  perhaps  better 
to  employ  lavage  two  or  three  times  in  the  week  than  to 
use  it  each  day.  Where  excessive  quantities  of  fluid 
are  used,  distension  of  the  colon  occurs  and  may  be 
followed  by  troublesome  atony. 

In  some  persons  who  are  victims  of  a  chronic  infection 
of  the  intestine  with  putrefactive  anaerobes  the  intelli- 
gent application  of  the  foregoing  measures  suffices  to 
bring  about  a  high  grade  of  improvement.  The  chances 
of  obtaining  a  rapid  amelioration  of  symptoms  are 
greatest  in  those  persons  in  whom  the  process  has  not 
been  one  of  long  standing.  The  factor  of  duration  of  the 


338      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

infection  appears  to  me  fully  as  important  as  its  intensity. 
It  is  doubtless  true  that  many  patients  suffering  from 
neurasthenic  symptoms  with  mental  depression  or 
moderate  anaemia,  have  been  benefited  by  ordinary 
therapeutic  measures  suggested  by  experience  and  com- 
mon sense,  but  not  consciously  directed  by  the  physician 
toward  the  control  of  the  putrefactive  conditions  in  the 
intestinal  tract.  The  recoveries  in  these  cases  have  often 
been  temporary  in  character,  for,  as  already  mentioned, 
there  is  a  strong  tendency  for  relapses  to  occur.  Con- 
siderable improvement  may  follow  a  second  course  of 
treatment,  and  a  third  or  fourth,  but  after  a  time  it  is 
noticed  both  by  the  patient  and  his  physician  that 
relapses  occur  more  readily  than  formerly;  i.e.  in  re- 
sponse to  apparently  more  trivial  errors  of  living.  It 
is  also  noticeable  that  although  the  correction  of  these 
errors  in  living  is  still  followed  by  improvement,  the 
improvement  is  not  so  rapid  and  the  periods  of  rest  and 
recreation  and  careful  living  are  less  beneficial  than 
was  formerly  the  case.  This  may  lead  to  discourage- 
ment. It  is  certainly  true  that  the  physician  must 
be  extremely  cautious  about  venturing  a  prognosis  in 
those  cases  of  chronic  excessive  intestinal  putre- 
faction that  are  not  merely  of  long  standing  but  have 
had  the  benefit  of  intelligent  medical  treatment  and 
long  periods  of  exemption  from  depressing  conditions 
of  living.  The  prognosis  is  best  in  those  persons  whose 
symptoms  have  not  only  been  of  moderate  duration  but 
who  have  had  little  opportunity  to  care  for  themselves  — 
persons  who  have  continued  actively  at  work  and  have 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      339 

committed  gross  errors  in  diet,  in  sexual  life,  etc.  The 
removal  of  the  obviously  injurious  conditions  in  these 
cases  is  almost  always  followed  by  a  quick  and  satis- 
factory improvement,  provided  the  patient  be  not 
burdened  by  significant  neurotic  taints  or  has  not 
developed  a  considerable  degree  of  ansemia.1  In  persons 
who  have  had  the  benefit  of  much  rest  and  recreation 
and  have  cared  for  themselves  under  luxurious  conditions 
of  living,  the  outlook  is  much  less  promising  because  in 
many  of  these  cases  most  of  the  ordinary  therapeutic 
measures  have  already  been  exhausted.  It  should  be 
remembered,  however,  that  even  in  such  cases  a  period 
of  rest  of  one  or  two  years  under  favorable  conditions 
may  bring  about  a  great  change  in  physical  state,  while 
short  periods  of  rest  show  very  little  effect  on  the  patient. 
For  those  who  find  it  very  difficult  to  follow  in  a  rational 
way  the  advice  of  a  physician,  owing  to  inability  to  exert 
the  necessary  self-control,  a  period  of  residence  in  a  good 
sanitarium  under  the  immediate  supervision  of  a  tactful 
and  intelligent  practitioner  may  do  much  more  good 
than  home  treatment.  Similarly  a  cure  at  Carlsbad 
under  rigid  conditions  of  diet  and  general  hygiene  may 
be  of  very  distinct  benefit  in  reducing  the  manifestations 
of  a  chronic  anaerobic  infection  of  the  intestine. 

In  extreme  cases  of  chronic  excessive  intestinal 
putrefaction  in  which  nearly  everything  has  been  tried 

1 1  regard  the  presence  of  a  high  degree  of  ansemia  and  the  per- 
sistence of  a  high  grade  of  infection  with  the  gas-bacillus  as  bad 
prognostic  signs,  especially  if  associated  with  a  persistently  intense 
dimethylamidobenzaldehyde  reaction  of  the  urine. 


340      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

that  can  be  suggested  by  competent  medical  men,  the 
question  of  surgical  interference  may  arise.  The  past 
ten  years  have  recorded  a  very  large  number  of  surgical 
triumphs  in  connection  with  the  human  digestive  tract. 
Unfortunately  in  a  majority  of  the  instances  of  disease 
successfully  relieved  by  surgical  methods  little  or  nothing 
is  known  of  the  bacterial  conditions  in  the  digestive 
tract  and  what  modifications  they  may  have  undergone 
as  a  result  of  treatment.  There  can  be  no  doubt,  how- 
ever, that  in  some  of  the  cases  that  have  been  success- 
fully subjected  to  operation  a  part  at  least  of  the  im- 
provement has  come  about  through  the  mitigation  of 
putrefactive  processes  in  the  large  intestine.  It  is,  I  think, 
extremely  desirable  that  much  closer  attention  should 
be  given  to  the  study  of  cases  from  the  bacterial  stand- 
point than  has  ever  been  the  case,  for  the  knowledge 
which  must  surely  be  accumulated  in  this  way  must 
prove  extremely  helpful  in  deciding  what  shall  be  done 
with  certain  patients  suffering  from  chronic  anaerobic 
infections  of  a  severe  type.  An  operation  which  has  been 
very  often  practiced  in  one  or  another  form  is  that  of 
gastro-enterostomy.  In  cases  of  dilatation  of  the  stomach 
which  have  resisted  ordinary  forms  of  treatment,  ad- 
mirable results  have  many  times  been  obtained  in  the 
relief  of  a  great  variety  of  digestive  disturbances.  It 
seems  highly  probable  that  the  relief  afforded  in  these 
cases  has  been  due  in  most  instances  in  part  at  least  to  the 
greatly  improved  conditions  of  bacterial  activity  which 
followed  the  removal  of  a  source  of  stagnation  and 
putrefaction  in  the  upper  part  of  the  digestive  tract. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      341 

The  pyloroplastic  operations  have  also  frequently  been 
followed  by  striking  benefit  in  chronic  conditions. 
Even  in  cases  where  an  operation  is  done,  not  so  much 
for  dilatation  of  the  stomach  as  for  a  spastic  or  hyper- 
trophic  condition  at  the  pylorus,  the  improvement  may 
have  been  associated  with  a  diminished  excretion  of  the 
ethereal  sulphates.  I  recall  one  case  in  which  the 
ethereal  sulphates  had  regularly  run  far  in  excess  of 
the  normal  but  in  which  this  excess  promptly  disap- 
peared after  a  pyloroplastic  operation  done  for  the  relief 
of  a  gradually  increasing  stenosis  of  the  stomach  as- 
sociated with  hyperchlorhydria  and  periodical  seizures 
of  vomiting.  Here  the  relief  from  putrefactive  decom- 
positions was  probably  merely  one  incident  of  ameliora- 
tion of  more  acute  and  pressing  conditions.  Looking  at 
the  pyloroplastic  and  similar  operations  from  the  stand- 
point of  chronic  putrefactive  intestinal  disorders,  one 
has  to  admit  that  the  indications  for  such  operations  are 
at  present  not  entirely  clear. 

The  operations  to  which  reference  has  just  been  made 
are  designed  to  secure  the  prompt  emptying  of  the 
stomach  into  the  small  intestine.  An  entirely  different 
type  of  operation  and  one  which  has  as  yet  been  seldom 
performed  relates  to  the  attempt  to  exclude  a  portion  of 
the  large  intestine.  The  fact  that  the  large  intestine 
is  the  seat  of  some  of  the  most  distressing  derangements 
associated  with  putrefaction  strongly  suggests  the  pos- 
sibility that  these  putrefactive  disorders  maybe  mitigated 
by  surgical  procedures  which  have  for  their  aim  the 
elimination  of  a  portion  of  the  colon.  Operations  with 


342      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

this  end  in  view  have  in  a  number  of  instances  been 
practiced,  but  not,  so  far  as  I  am  aware,  with  the  primary 
object  of  greatly  reducing  the  opportunities  for  intestinal 
putrefaction.  The  value  of  such  procedures  is  therefore 
as  yet  largely  a  matter  of  conjecture.  That  the  elimina- 
tion of  the  large  intestine  would  be  followed  by  a  very 
great  reduction  in  the  absorption  and  excretion  of  pro- 
ducts of  decomposition  must  be  regarded  as  certain. 
The  experiments  which  have  been  made  by  Baumann 
and  others  on  dogs  in  which  a  fistula  in  the  ileum  had 
been  established,  leave  no  room  for  doubt  that  putre- 
faction is  greatly  decreased  by  such  a  procedure.1  The 
closure  of  the  fistula  and  the  reestablishment  of  the 
natural  paths  have  been  in  such  cases  promptly  followed 
by  a  renewed  excretion  of  the  ethereal  sulphates.  Aside 
from  the  surgical  difficulties  incidental  to  operations 
designed  to  shorten  the  large  intestine  there  are  two 
possibilities  of  a  disadvantageous  outcome  which  will 
have  to  be  tested  by  future  experience.  One  of  these 
is  the  possible  detrimental  influence  of  such  a  shortening 
of  the  gut  upon  the  processes  of  nutrition.  It  is  claimed 
by  some  physiologists  that  the  processes  of  peptoniza- 
tion  and  absorption  continue  to  be  carried  on  in  no 
unimportant  degree  in  the  large  intestine,  and  hence  that 
an  elimination  of  a  considerable  portion  of  this  part  of 

1  In  a  dog  whose  ileum  was  inserted  a  few  inches  above  the 
rectum  the  ethereal  sulphates  were  low  but  the  indican  reaction 
(on  a  meat  diet)  was  intense.  This  animal  was  prepared  for  use 
by  Dr.  Carrel  of  the  Rockefeller  Institute.  The  fluid  faeces  con- 
tained indol.  After  the  operation  there  was  a  considerable  gain  in 
weight  on  a  strict  meat  diet. 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      343 

the  digestive  tract  must  necessarily  be  followed  by  some 
failure  in  nutrition.  I  question  whether  the  latter  part 
of  this  contention  is  justified ;  for  while  some  digestive 
action  cannot  be  denied  to  the  large  intestine,  there  are 
many  reasons  for  thinking  that  by  far  the  larger  part  of 
the  nutritive  resorption  necessary  for  the  maintenance 
of  a  good  state  of  nutrition  occurs  above  the  ileocsecal 
valve.  Even,  however,  if  it  be  ordinarily  true  that  a 
significant  amount  of  material  is  absorbed  from  the 
region  beyond  the  ileocsecal  valve,  there  is  no  reason 
why  such  absorption  cannot  under  special  conditions 
be  relinquished  without  detriment  to  nutrition.  Even 
the  partial  artificial  peptonization  of  proteids  would 
do  much  to  secure  an  adequate  absorption  of  such  food 
materials  above  the  ileocsecal  valve  and  in  cases  of  long- 
continued  intestinal  intoxication  with  a  grave  prognosis, 
the  resort  to  permanent  peptonization  of  the  food  mate- 
rials would  certainly  be  the  substitution  of  a  lesser  for  a 
greater  evil.  Although  it  must  be  admitted  that  our 
knowledge  on  this  point  is  not  at  present  decisive,  I  am 
strongly  disposed  to  take  the  view  that  nutrition  could 
be  adequately  maintained  in  the  absence  of  the  greater 
part  of  the  large  intestine. 

Another  possibility  of  an  unfavorable  sort  relates  to  the 
inconvenience  incidental  to  the  rapid  passage  of  semi- 
solid  or  fluid  intestinal  contents.  It  seems  probable  that 
if  the  conditions  of  diet  were  carefully  studied,  any 
serious  difficulty  from  this  source  might  be  avoided. 
Moreover,  the  objection  just  mentioned  would  be  greatly 
minimized  by  connecting  the  ileum,  csecum,  or  trans- 


344      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

verse  colon  with  the  rectum  instead  of  making  a  com- 
munication in  the  abdominal  or  lumbar  region. 

It  is  to  be  remembered  that  operations  like  those  just 
discussed  would  seldom  be  undertaken  except  where 
life  is  in  danger  from  the  persistence  of  a  process  which 
has  been  unsuccessfully  treated  by  the  usual  hygienic 
and  medical  resources  of  the  physician.  There  are 
conditions  of  mental  depression  and  conditions  of 
anaemia  in  which  I  believe  an  operation  involving  the 
shortening  of  the  intestine  to  be  justified.  There  is 
much  to  be  said  in  favor  of  urging  operation  before  the 
establishment  of  extreme  conditions  of  deranged  function 
in  the  nervous  system  or  the  development  of  anaemia 
associated  with  greatly  impaired  regenerative  capacity  of 
the  blood.  It  is  easy  to  understand  that  by  too  long  wait- 
ing a  biological  situation,  susceptible  of  great  improve- 
ment by  timely  operation,  might  be  rendered  so  extreme 
that  the  recuperative  powers  of  the  damaged  cells  would 
not  suffice  to  restore  even  a  fair  degree  of  health. 

The  operation  of  connecting  the  vermiform  appendix 
with  the  outer  world  through  a  fistulous  opening  has 
been  repeatedly  performed  in  cases  of  chronic  dysentery, 
for  the  purpose  of  giving  patients  the  benefit  of  thorough 
irrigation  of  the  large  intestine.  It  is  possible  that  this 
operation  (which  might  entail  fewer  risks  to  the  patient 
than  operations  of  the  class  just  mentioned)  may  be 
worthy  of  trial  for  the  relief  of  chronic  intoxications 
leading  to  extreme  anaemia  or  to  serious  disorders  of 
the  nervous  system. 

The  possibility  of  checking  the  progress  of  specific 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      345 

bacterial  processes  in  the  intestinal  tract  by  means  of 
specific  bacterial  vaccines  or  through  the  use  of  specific 
bactericidal  sera  has  come  plainly  into  view  during  the 
past  ten  years.  Mention  has  already  been  made  of  the 
methods  that  have  been  employed  to  check  the  develop- 
ment of  infections  from  organisms  of  the  B.  coli  group 
and  closely  related  bacteria.  The  work  of  Sir  A.  E. 
Wright  upon  the  elevation  of  the  opsonic  index  in  cases 
of  local  staphylococcal  infections  and  in  the  case  of 
streptococcus  septicaemia  makes  it  not  improbable  that 
in  the  case  of  intestinal  affections  clearly  shown  to  be 
in  part  dependent  on  staphylococcus  or  streptococcus 
infection,  the  methods  of  vaccination  employed  by  him 
may  be  effective  in  increasing  the  phagocytic  defenses 
of  the  body  against  these  infective  agents.  Whether 
similar  methods  are  likely  to  be  of  service  in  relation  to 
such  cases  as  show  the  presence  of  well-defined  chronic 
infections  dependent  on  anaerobic  putrefactive  organ- 
isms such  as  B.  aerogenes  capsulatus  it  is  impossible  to 
predict.  It  has  been  already  mentioned  that  we  have 
not  as  yet  observed  any  instance  of  chronic  saccharo- 
butyric  putrefaction  (due  to  an  infection  with  B.  aero- 
genes  capsulatus)  hi  which  there  has  been  a  heightening 
of  the  agglutination  of  the  patient's  blood  with  the  infect- 
ing organisms.  This,  however,  does  not  prove  that 
specific  antibodies  are  never  formed  through  the  agency 
of  these  anaerobes  in  the  intestine.  There  are  in  fact 
some  experimental  observations  which  indicate  that  it 
is  possible  to  develop  a  specific  agglutinating  power  for 
B.  aerogenes  capsulatus.  Whether  the  ability  of  the 


346      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

leucocytes  to  take  up  these  organisms  suffers  any  diminu- 
tion in  chronic  infections  is  not  yet  known;  hence 
speculations  as  to  the  beneficial  influence  of  the  use  of 
vaccines  prepared  from  B.  aerogenes  capsulatus  are  use- 
less. It  is  likely  that  this  phase  of  study  will  receive 
attention  before  long. 


SOCIOLOGICAL  CONSIDERATIONS 

IT  is  hardly  satisfying  to  conclude  this  consideration 
of  the  infections  of  the  digestive  tract  without  some 
reference  to  their  sociological  bearings.  The  medical 
practitioner  too  often  is  forced  to  deal  exclusively  with 
damage  done  —  damage  of  an  irreparable  character. 
He  is  unable  to  grapple  with  the  weighty  problem  of 
preventing  disease.  In  modern  civilized  communities 
the  task  of  prevention  has  fallen  into  the  hands  of 
health  boards.  Where  these  have  been  guided  by 
highly  intelligent  and  trained  men,  unselfishly  devoted 
to  the  public  good  (as  has  lately  been  the  case  hi  New 
York  City),  there  has  resulted  a  noteworthy  diminution 
in  the  death  rates.  This  is  true  of  many  kinds  of  disease, 
but  applies  with  great  distinctness  in  the  case  of  the  mor- 
tality of  infants  from  diarrhoeal  disorders.  The  infant 
mortality  from  such  disorders  is  due  mainly  to  the  bac- 
terial contamination  of  milk,  and  some  municipal  author- 
ities have  lately  been  able  to  insist  on  the  systematic  re- 
jection of  bad  milk.  The  decline  in  deaths  from  summer 
diarrhoeas  is  a  result  of  this  improved  milk  sanitation. 

The  health  boards  have,  however,  only  begun  their 
task.  It  is  certain  that  the  beneficent  work  of  preven- 
tion will  in  time  grow  so  efficient  as  to  make  the  fatal 
milk  infections  of  infancy  comparatively  rare,  provided 
something  be  also  done  to  raise  the  intelligence  of  pa- 

347 


348      INFECTIONS  OF  THE  DIGESTIVE  TRACT 

rents.  Equally  preventable  are  the  majority  of  cases 
of  typhoid  fever.  It  is  not  because  of  any  lack  of 
hygienic  knowledge  that  typhoid  fever  yearly  claims 
its  hundreds  of  victims  in  the  United  States.  It  is 
because  of  the  semi-criminal  indifference  of  the  un- 
educated politicians  who  rule  many  of  our  great  cities. 
Eradicate  the  sources  of  typhoid  contamination  of  the 
water  supplies  of  cities,  and  the  deaths  from  typhoid 
fever  will  dwindle  to  insignificant  numbers.  One  highly 
competent  and  determined  publicist  who,  backed  by  pub- 
lic opinion,  should  force  the  rulers  of  our  cities  to  give 
the  people  uncontaminated  water,  would  do  more  for  his 
country  than  the  hundreds  of  physicians  who  are  con- 
stantly engaged  in  the  treatment  of  typhoid  fever. 

But  the  problem  of  prevention  will  have  been  only 
partially  solved  when  the  infections  of  cholera  infantum, 
dysentery,  and  typhoid  fever  are  broadly  checked  by 
measures  based  upon  what  modern  medicine  has  taught 
us  about  the  causes  of  these  diseases.  There  will  re- 
main the  more  elusive  task  of  preventing  the  occurrence 
of  the  severe  chronic  infections  of  the  digestive  tract. 
The  acute  infections  like  dysentery  and  typhoid  are  so 
numerous  and  obtrusive  in  their  manifestations  that  it 
is  impossible  to  overlook  them;  the  chronic  infections 
are  insidious  in  their  onset,  obscure  in  their  manifesta- 
tions, and  seldom  involve  groups  of  individuals ;  hence 
they  pass  relatively  unnoticed.  The  injurious  effects 
of  the  chronic  infections  are  none  the  less  real.  They 
restrict  the  fullest  development  of  a  nation  by  shortening 
the  lives  of  many  useful  individuals  and  by  rendering 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      349 

many  distinctly  less  productive  than  if  these  persons 
attained  physical  vigor  more  nearly  in  accord  with  their 
inherent  possibilities.  These  partial  failures  of  per- 
formance entail  a  severe  economic  loss  to  the  community 
in  which  they  occur.  But  this  loss  is  one  that  cannot 
be  adequately  measured  in  dollars  and  cents,  for  it  must 
make  a  nation  less  efficient  in  art,  in  science,  in  letters, 
and  in  all  intellectual  pursuits.  And,  finally,  it  must  not 
be  forgotten  that  the  chronic  enterogenic  intoxications 
of  the  nervous  system  may  be  extremely  detrimental 
to  character  and  contribute  to  complicate  and  mar  the 
finer  human  relations. 

It  is  tacitly  assumed  by  many  that  these  various 
morbid  manifestations  are  inevitable,  are  inherited,  or 
are  in  some  other  way  an  expression  of  the  will  of  Provi- 
dence. The  conditions  to  which  I  refer  are  indeed 
recognized  by  few  persons  to  be  what  they  actually  are 
—  the  effects  of  chronic  poisoning  of  gastro-enteric 
origin.  Nevertheless  it  is  certain  that  these  relatively 
obscure  physical  conditions  are  in  large  measure  pre- 
ventable. But  their  prevention  is  not  simple;  for  it 
implies,  first,  the  recognition  of  chronic  infections  of  the 
digestive  tract  (in  which  the  putrefactive  anaerobes 
are  prominently  concerned)  capable  of  slowly  damag- 
ing the  cell  potentialities  upon  which  health  depends, 
and,  secondly,  it  involves  the  recognition  and  control  of  a 
series  of  causative  or  favoring  elements,  such  as  habitual 
errors  in  diet,  sedentary  habits,  excessive  mental  and 
physical  work,  emotional  fatigue,  errors  in  sexual  life,  etc. 

The  recognition  of  the  presence  of  a  chronic  intestinal 


350       INFECTIONS  OF  THE  DIGESTIVE  TRACT 

infection  (as  by  B.  aerogenes  capsulatus)  is  not  in  itself 
difficult,  but  necessitates  patient  inquiry  and  a  knowledge 
of  methods  of  investigation  on  the  part  of  the  physician. 
The  methods  of  investigating  the  digestive  tract  which 
have  been  briefly  outlined  in  this  volume  must  prove 
valuable  in  enabling  the  practitioner  to  determine  the 
presence  of  abnormal  bacterial  processes  before  the  onset 
of  the  clinical  signs  of  incurable  or  highly  refractory 
states  of  intoxication. 

The  control  of  the  causal  and  favoring  factors  in  the 
establishment  of  chronic  intoxications  is  partly  the  duty 
of  the  physician.  It  is,  however,  a  duty  which  it  is 
unreasonable  to  expect  him  to  discharge  fully  under  the 
conditions  existing  to-day,  no  matter  how  capable  and 
willing  he  may  be.  It  is  not  possible  for  any  practitioner 
to  undertake  the  entire  education  of  his  patients  in 
respect  to  knowledge  of  hygiene,  or  to  develop  their 
will  power  to  the  point  where  such  knowledge  becomes 
practically  efficient.  Yet  this  is  what  he  must  do  to- 
day if  he  would  achieve  a  high  degree  of  success  in  the 
prevention  of  the  worst  consequences  of  the  chronic 
infections  of  the  digestive  tract.  Before  he  can  become 
ideally  efficient  as  a  physician  he  must  have  the  intelli- 
gent cooperation  of  parents  and  educational  institutions. 

Education  in  the  facts  of  hygiene  and  in  the  practice  of 
intelligent  self-control  cannot  be  acquired  in  a  few  hours, 
but  necessitates  years  of  appropriate  teaching  in  home 
and  school.  So  long  as  the  schools  and  universities 
almost  wholly  fail  to  fit  their  pupils  to  meet  even  the 
most  obvious  requirements  of  practical  life,  so  long  will 


INFECTIONS  OF  THE  DIGESTIVE  TRACT      351 

it  be  impossible  to  avoid  great  losses  of  energy  and  other 
unhappy  consequences  of  the  chronic  intoxications. 
At  present  the  schools  look  to  parents  to  instruct  their 
children  in  the  supposedly  simple  matters  of  regulating 
eating  and  drinking,  exercise,  habits  of  work,  and  sexual 
habits,  while  the  parents  vaguely  hope  (if  they  think 
at  all  about  such  matters)  to  be  relieved  of  these  embar- 
rassing duties  through  the  schools.  The  truth  is  that 
neither  parents  nor  schools  are  to-day  able  to  give  this 
much  needed  sort  of  education.  The  remedy  must 
be  provided  by  the  schools,  which  in  their  eagerness 
to  impart  conventionalized  facts  are  now  quite  blind  to 
some  of  the  most  pressing  needs  of  their  pupils.  Through 
the  schools  and  universities  (or  other  appropriate 
organizations)  the  parents  of  the  future  must  be  educated 
both  as  to  the  facts  and  the  moral  aspects  of  bodily 
hygiene.  The  physician  will  thus  be  enabled  to  do  better 
work  in  the  prevention  of  some  of  the  most  distressing 
human  ailments.  And  it  seems  not  unreasonable  to 
hope  that  some  of  the  lessons  now  learned  only  by  bitter 
experience,  after  much  that  is  best  in  life  has  been 
sacrificed  to  ignorance  and  uncurbed  impulse,  will  be 
assimilated  sufficiently  early  in  life  to  mitigate  materially 
the  lot  of  a  not  inconsiderable  part  of  mankind.  I 
believe  the  lengthening  of  the  span  of  human  life  to  be 
among  the  attainable  results  of  such  teaching.  Is  it 
not  likely  that  as  men  grow  wiser  an  increasing  number 
will  deliberately  strive  so  to  regulate  their  lives  as  to 
improve  the  expectation  of  crowning  well-spent  days 
with  the  peculiarly  fine  satisfactions  of  old  age  ? 


INDEX 


Acetone,  218;  formation,  in  bac- 
terial cultures,  136. 
Acid,  acetic,  product  of  bacte- 
rial activity,  8;  in  bottle-fed 
babies,  65  ;  in  healthy  animals, 
66. 

butyric,     production    in    putre- 
faction,   218;     by    anaerobes, 
293;  by  B.  butyricus,  46;  from 
lactic  acid,  22;  in  mouth,  29, 
30,  300 ;  in  stomach,  30. 
caproic,  293,  294. 
glycerophosphoric,  222. 
indol-acetic,  243. 
indol-amido-propionic,  243. 
indol-propionic,  244. 
lactic,  22. 
oxalic,  216. 
propionic,  218,  293. 
skatol-amido-acetic,  243. 
valeric,  293. 

Acid  formation,  in  bottle-fed 
babies,  67;  in  fermentation, 
215. 

Acids,  volatile  fatty,  21. 
Acidophile  bacteria,  11. 
Adult  life,  bacteria  in  intestines,  72. 
Aerobic  and  anaerobic  conditions, 
in  digestive  tract,  23;    in  in- 
testine,  31 ;    in  stomach,   30 ; 
tested  by  methylene  blue,  34. 
Age,  effect  on  intestinal  bacteria, 

35. 

Aggressins,  160  ;  in  dysentery,  174. 
Alcohol,     formation     in     bacterial 

cultures,  8,  136. 
Amines,  220. 

Ammonia,    formation   in   bacterial 
cultures,   136,  220;    in  bottle- 
fed  children,  66,  67. 
Ammonium  butyrate,  295,  299. 
Anemia,    in   saccharo-butyric    pu- 
trefaction, 303. 


Anaerobic  bacteria,  191 ;  action 
on  bilirubin,  294;  action  on 
proteids,  24 ;  in  bottle-feeding, 
60,  63  (footnote);  with  diet 
of  bread,  87;  in  caries  of 
teeth,  29;  growth  in  intestine 
of  cats,  80,  81;  influence  of 
reaction  on  growth  and  prod- 
ucts, 21 ;  obligate,  24 ;  patho- 
genicity,  117;  putrefactive, 
10;  reduction  of  numbers  by 
treatment,  329;  in  saccharo- 
butyric  putrefaction,  279,  291 ; 
spore-bearing,  6. 

Anaerobic  life,  definition,  25. 

Animals,  bacteria  in  intestines,  80 ; 
relative  duration  of  life,  85. 

Anthrax  bacillus,  162. 

Anthrax,  symptomatic,  formation 
of  indol,  243. 

Aromatic  products  of  putrefactive 
decomposition,  237. 

Autolysis,  1. 

Autotoxins,  18. 

Autotoxin  theory,  17-19. 

Bacillac,  334,  335. 

Bacillus,  acidolacticus,  207,  244,  335. 
acidophilus,  11 ;  in  bottle-fed 
children,  62;  in  nurslings,  38; 
protective  action,  11. 
aerogenes  capsulatus,  2  (foot- 
note), 6,  11,  25,  196,  197;  in 
acute  inflammation  of  the 
ileum,  206;  in  adult  life,  74; 
agglutinating  action,  199;  in 
anaerobic  cultures,  117;  in 
animals,  82 ;  biochemical 
properties,  208;  in  bottle-fed 
children,  63;  in  carnivorous 
animals,  80 ;  in  childhood  and 
adolescence,  70;  cultural  in- 
vestigation, 116;  different 


353 


354 


INDEX 


Bacillus  — 

names,  45  (footnote) ;  different 
strains,  198,  199;  gas  for- 
mation, 201,  203;  growth  in 
fermentation  tubes,  127,  130; 
growth  in  milk,  117;  hsemo- 
lytic  action,  203,  303;  mor- 
phology, 200 ;  in  nurslings,  39, 
45;  in  pernicious  anaemia, 
312;  relation  to  indicanuria, 
261,  263;  in  saccharo-butyric 
putrefaction,  291,  293,  294, 
298;  toxins  acting  on  nervous 
system,  205 ;  in  senescence,  78 ; 
studied  by  incubation  method, 
118-124;  in  tiger  with  osteo- 
malacia,  81. 

alkaligenes,  24,  28. 

anthracis,  162. 

anthracis  symptomatici,  24,  118, 
209. 

bifidus,  5,  10,  17,  113,  190; 
anaerobic  cultures,  116;  in 
bottle-fed  children,  62;  in 
childhood  and  adolescence,  70 ; 
growth  in  fermentation  tubes, 
131 ;  infection  through  anus, 
56 ;  in  marasmus,  288 ;  in 
meconium,  57 ;  morphology,  41 
and  footnote ;  in  nurslings,  38. 

botulinus,  6,  118,  210. 

butyricus  (Botkin),  45. 

cloacae,  63,  117. 

coli  communis,  5,  8,  14  et  seq. ; 
in  adult  life,  74;  in  animals, 
82;  antagonism  to  other  bac- 
teria, 7 ;  in  bottle-fed  children, 
60;  characteristics,  7;  de- 
fensive action,  10,  12;  dis- 
appearance from  intestine  in 
disease,  156;  effect  of  dif- 
ferent diets,  87;  in  gastric 
ulcer,  154;  growth  in  fermen- 
tation tubes,  130;  indol  for- 
mation, 243,  262,  264,  279, 
280,  281;  in  intestinal  putre- 
faction, 155;  in  meconium, 
56;  in  nurslings,  49;  number 
diminished  in  saccharo-butyric 
putrefaction,  292 ;  pathogenity, 
150;  production  of  hydrogen 
sulphide,  229. 


Bacillus  — 

coli  group,  9;  defensive  action, 
9,  10;  in  nurslings,  39;  in 
senescence,  75,  76. 

dysenteries,  6,  101,  172;  effect 
of  toxins  on  nervous  system, 
180;  immunizing  sera,  175; 
lesions  due  to  elimination  of 
poison,  178 ;  polyvalent  serum, 
176. 

of  Eberth,  see  B.  typhi. 

entericus,  184. 

enteritidis  sporogenes,  45  (foot- 
note), 169,  197,  208. 

fcecalis  alcaligenes,  158  (foot- 
note), 169. 

flavosepticum,  159. 

Flexneri,  15. 

fluorescens,  14. 

fluorescens  non  liquefaciens,  28. 

of  Friedlander,  14. 

of  Kruse,  15. 

lactis  aerogenes,  5,  7,  15,  16,  24, 
31 ;  in  bottle-fed  children,  62 ; 
characteristics,  8 ;  hydrogen 
sulphide  formation,  229;  in 
nurslings,  49;  pathogenicity, 
153. 

liquefaciens  ilei,  70  (footnote), 
113. 

mascerans,  220. 

cedematis  maligni,  24,  118,  292, 
319. 

paralacticus,  207. 

paraputrificus,  193. 

paratyphoid,  6. 

perfringens,  11,  45  (footnote), 
197,  207. 

of  plague,  162. 

prodigiosits,  14,  15,  16. 

proteus  vulgaris,  5,  14,  24,  182, 
183,  244. 

putrificus,  6,  14,  24,  25,  192,  204 ; 
in  adult  life,  74 ;  in  bottle-fed 
children,  63;  in  caries  of 
teeth,  195 ;  on  fruits,  319 ;  in- 
dol formation,  279,  282  (foot- 
note) ;  mercaptan  formation, 
195,  297 ;  in  nurslings,  44 ;  rela- 
tion to  indicanuria,  263;  in 
saccharo-butyric  putrefaction, 
291,  297. 


INDEX 


355 


Bacillus  — 

pyocyaneus,  14,   15,  16;    growth 
in    fermentation    tubes,     132; 
in  intestines  in  health,  103. 
of  quarter  evil,  see  B.  anthracis 

symptomaticus. 
of  rauschbrand,  see  B.  anthracis 

symptoma  tici. 
of  Shiga-Kruse,  15. 
subtilis,  56. 

typhi,  6,  10,  15,  102,  157. 
violarius  acetonicus,  220. 
Welchii,    see    B.    aerogenes   cap- 

sulatus. 

Bacteria,  anaerobic,  191. 
in  excreta,  1  and  footnote, 
in  intestines,  in  adult  life,  72; 
in  animals,  80;  buffalo,  83; 
camel,  82;  carnivorous  ani- 
mals, 82;  cat,  80;  elephant, 
82;  herbivorous  animals,  82; 
horse,  82 ;  lion,  81 ;  wolf,  81 ; 
classification,  105 ;  autopsy, 
normal  boy,  70  (footnote) ; 
at  different  ages,  35,  60; 
distribution,  7;  elective  an- 
tagonistic action,  14;  influence 
of  food,  86;  in  health,  1,  4; 
obligate,  7;  their  significance, 
5 ;  pathogenic  forms  in  health, 
102. 

liquefying,  181. 
in  milk,  60. 
Bail,  160,  165. 
Baldwin,  216. 
Basic  substances,  221. 
Bauer,  146,  147,  149  (footnote). 
Baumann,  241. 

Baumann  and  Udranzky,  224,  225. 
Baumstark,  146. 
Beijerink,  26. 
Bergh,  235. 
Bergman,  4. 
Bernard,  Claude,  243. 
Betz,  231. 

Bienstock,  14,  24,  44,  192,  193,  194. 
Bilirubin,  reduction  by  anaerobes, 

294. 

Bjeloussow,  11. 
Blair,  86. 
Blumenthal,  247. 
B6cai,  222. 


Booker,  186. 
Botkin,  45. 
Botulism,  211. 
Boycott,  29. 
Breaudat,  220. 
Brieger,  224,  225. 
Bryant,  99. 

Burgeon  treatment,  232. 
Butyric  acid,  see  Acid,  butyric. 
Butyric  acid  bacillus  in  bottle-fed 
children,  63. 

Cadaverin,  220,  224,  226. 

Caprice  acid,  293,  294. 

Carbon  dioxide  in  saccharo-butyric 
putrefaction,  294. 

Caries  of  teeth,  29. 

Carnivorous  animals,  pathogenic- 
ity  of  faecal  flora,  82. 

Champagne,  producing  urticaria 
and  gout,  276,  285. 

Chantemesse,  162. 

Charrin  and  Roget,  95. 

Children,  bottle-fed,  bacteria  in 
intestines,  59 ;  anaerobic 
forms,  50,  61 ;  distribution,  61 ; 
products  of  decomposition,  64. 

Cholin,  220,  222,  223,  224. 

Citron,  161. 

Classification  of  bacteria  in  digest- 
ive tract,  105 ;  by  agglutinins, 
110 ;  by  biochemical  properties, 
106;  by  morphology,  106;  by 
motility,  106 ;  by  pathogenicity, 
108 ;  by  spore  formation,  109 ; 
by  staining  properties,  106. 

Clemens,  148. 

Clinical  types  of  enterogenous 
poisoning,  274. 

Collins,  110,  336. 

Colon,  anaerobic  conditions,  33; 
number  of  bacteria,  33. 

Colon  bacillus,  see  B.  coli. 

Colon  irrigation,  influence  on  pu- 
trefactive processes,  337. 

Colon-typhoid-dysentery  group  of 
organisms,  150. 

Conradi  and  Kurpjuweit,  9,  15, 
37,  18,  20. 

Cresol,  237,  246. 

Gushing  and  Livingston,  31. 

Cyanosis,  enterogenic,  234-236. 


356 


INDEX 


Cyclical  vomiting,  277. 
Cystin,  229. 
Cystinuria,  224. 

Defensive  action  of  digestive 
juices,  6. 

Diamines,  220,  224. 

Diarrhoea,  from  saccharo-butyric 
putrefaction,  301. 

Dibenzoylcadaverin,  225. 

Digestive  juices,  defensive  action, 
6. 

Dimethylamidobenzaldehyde  reac- 
tion, in  faeces,  145;  in  maras- 
mus, 286 ;  with  skatol,  240 ;  in 
urine,  147. 

Diplococci,  in  marasmus,  288;  in 
mucous  colitis,  101 ;  in  per- 
nicious anaemia,  188;  in 
saccharo-butyric  putrefaction, 
291,  292,  305. 

Diplococcus  intestinalis,  15,  16. 

Distribution  of  bacteria  in  in- 
testines, 7. 

Doebert,  158  (footnote). 

Dopter,  180. 

Dunham,  106,  110,  197. 

Duval,  103. 

Dysentery  bacilli,  see  B.  dysenterice. 

Eberle,  51. 

Eberth's  bacillus,  157. 

Ehrlich,  147,  148,  275. 

Ehrlich  aldehyde  reaction,  see  Di- 
methylamidobenzaldehyde re- 
action. 

Ellinger,  226 

Emminghaus,  231. 

Enterogenic  cyanosis,  234,  236. 

Enterogenous  poisons,  individual 
susceptibilities,  274. 

Enzymes,  in  cellulose,  5 ;  tryptic,  6. 

Epileptic  seizures,  With  indicanuria, 
276. 

Epithelial  cells  of  digestive  tract, 
91 ;  effect  of  excessive  desqua- 
mation,  92 ;  protection  against 
indol,  93. 

Escherich,  10,  38,  39,  49,  55,  56, 
151,  186. 

Ethereal  sulphates,  72,  297;  in 
adult  life,  74 ;  in  childhood,  72 ; 


Ethereal  sulphates  — 

influence  of  colon  irrigation, 
337;  in  marasmus,  286;  re- 
duced by  lactic  acid,  244; 
in  saccharo-butyric  putrefac- 
tion, 296. 

Exhaustion,  influence  on  bacterial 
penetration  in  intestinal  tract, 
95. 

Fatigue,  in  excessive  intestinal 
putrefaction,  286;  in  indol 
and  phenol  poisoning,  289; 
in  marasmus,  289. 

Fatty  acid  formation  in  bacterial 
cultures,  136. 

Fatty  acids,  molecular  weights, 
136 ;  in  saccharo-butyric  pu- 
trefaction, 295. 

Ferment,  peptic,  6. 

Fermentation  tubes,  study  of  bac- 
teria, 126;  study  of  sediment, 
130. 

Fermentative  processes,  214. 

Ficker,  95. 

Flexner,  172,  175,  178,  180,  198, 
206. 

Fliigge,  45. 

Food,  184;  influence  on  intestinal 
bacteria,  86. 

Foster,  139. 

Fraenkel,  11,  197. 

Gaffsky,  157. 

Gartner,  169. 

Gas  formation,  by  mixed  faecal 
flora  from  nurslings,  66;  in 
saccharo-butyric  putrefaction, 
292. 

Gasphlegmon  bacillus,  see  B.  aero- 
genes  capsulatus. 

Gas  production,  influence  of  diet, 
129 ;  significance  of  diminu- 
tion, 128. 

Gelatin,  use  in  indicanuria,  267. 

Glycerophosphoric  acid,  222. 

Gram-negative  bacteria,  37. 

Gram-positive  bacteria,  37. 

Gram  stain,  value  of,  111-114. 

Granulo-bacillus  immobilis  lique- 
faciens,  45  (footnote),  125, 
196. 


INDEX 


357 


Grassberger,  45  (footnote). 
Grassberger  and  Schattenfroh,  125, 

197. 
Guanidin,  221. 

Haemolytic  action  of  faecal  ex- 
tracts, 302. 

Headache,  with  indicanuria,  277. 

Hemiparasites,  162. 

Herbivorous  animals,  bacteria  in 
intestines,  82 ;  development  of 
anaemia,  85 ;  pathogenicity  of 
faecal  flora,  83. 

Herter,  245. 

Herter  and  Foster,  139. 

Herter  and  Wakeman,  247. 

Hervieux,  271,  273. 

Hilgermann,  94. 

Hiss,  173,  174. 

Holt,  285. 

Hopkins,  242. 

Howard,  206. 

Howland,  248,  270. 

Hunger,  influence  on  bacterial 
penetration  through  intestinal 
walls,  95. 

Hydrobilirubin,  295;  Schmidt's 
reaction,  144. 

Hydrogen  formation  in  saccharo- 
butyric  putrefaction,  294. 

Hydrogen  sulphide,  227 ;  excretion 
in  urine,  231 ;  formation  by 
bacteria  in  animals,  80;  in 
bottle-fed  children,  67 ;  in 
enterogenic  cyanosis,  234-236 ; 
in  health,  230 ;  in  marasmus, 
230;  in  stomach,  229;  influ- 
ence on  organism,  230;  toxic 
action  on  dogs,  233. 

Hydrothionaemia,  230. 

Ileum,  anaerobic  conditions,  33 ; 
number  of  bacteria,  32. 

Indicanuria,  241, 246,  257,  278,  279, 
281;  in  adult  life,  74;  effect 
of  cathartics,  268;  of  colon 
irrigation,  337;  of  oxidizing 
substances,  332 ;  of  treatment, 
265 ;  experimental  production, 
261 ;  individual  symptoms, 
277;  in  occlusion  of  small  in- 
testine, 283;  relation  to  con- 


Indicanuria  — 

stipation,     263 ;     significance, 
258. 

Indigo,  246. 

Indigo  blue,  273. 

Indigo  red,  273. 

Indigouria,  271,  272. 

Indirubin,  273. 

Individual  susceptibilities  to  nitrog- 
enous poisons,  274. 

Indol,  7,  20,  241 ;  action  on  mus- 
cles, 254 ;  formation  by  bac- 
teria, from  bottle-fed  children, 
67 ;  in  cultures,  135 ;  in  child- 
hood and  adolescence,  72; 
in  nurslings,  53;  formation 
from  tryptophan,  243;  in 
marasmus,  284;  method  of 
determination,  138;  in  oc- 
clusion of  common  bile  duct, 
282;  in  occlusion  of  small 
intestine,  283;  in  pancreatic 
achylia,  283;  production  by 
B.  coli,  7,  8;  production  in 
bottle-fed  children,  64;  in 
saccharo-butyric  putrefaction, 
295,  299;  separation  from 
skatol,  139;  in  stools  in  ma- 
rasmus, 283;  toxic  action, 
242,  247-257. 

Indol-acetic  acid,  243. 

Indolaemia,  269. 

Indol-amido-propionic  acid,  243. 

Indolic  type  of  intestinal  putre- 
faction, 279,  280. 

Inclol-propionic  acid,  244. 

Indoluria,  269. 

Indoxyl,  271-272. 

Indoxyl-potassium-sulphate,  246. 

Intestinal  putrefaction,  see  Putre- 
faction, intestinal. 

Jaffe,  144. 

Kamen,  198,  199. 

Kedrowski,  27. 

Kefir,  334. 

Kikuchi,  175. 

Klein,  45  (footnote),  52,  115,  197, 

208. 

Kohn,  56. 
Kruse,  62,  173. 


358 


INDEX 


Kruse  and  Bail,  160. 

Kumyss,  335. 

Kurpjuweit,  9,  10,  15,  17,  18,  20. 

Lactic  acid,  22. 

Lactic  acid  bacillus,  207,  244,  335. 

Lecithin,  222,  223. 

Lee,  254. 

Lembke,  88. 

Levin,  2,  4. 

Libbman,  62. 

Livingston  and  Gushing,  31. 

Lubenau,  184. 

Lumbago,  276. 

Malzushita,  26. 

Manteufel,  18. 

Marasmus,  17;  bacteria  in  intes- 
tines, 287;  B.  bifidus,  287; 
ethereal  sulphates,  286;  indol 
formation,  284;  phenol  for- 
mation, 236;  symptoms,  285; 
treatment,  289. 

Matzoon,  334. 

Maury,  250. 

Meat,  reducing  action,  89. 

Meconium,  17;  bacterial  infection, 
56;  B.  aerogenes  capsulatus, 
57;  B.  bifidus,  57;  B.  coli 
communis,  56 ;  B.  subtilis,  56 ; 
physiological  functions,  59. 

Melancholia,  from  excessive  in- 
testinal putrefaction,  308. 

Mental  depression,  with  indican- 
uria,  277. 

Mercaptan,  30,  226;  formation  in 
bacterial  cultures,  137;  in 
bottle-fed  children,  67;  in 
carnivorous  animals,  82;  in 
herbivorous  animals,  80,  83; 
in  saccharo-butyric  putrefac- 
tion, 297;  method  of  deter- 
mination, 137. 

Mereschkowsky,  11. 

Metchnikoff,  78,  335. 

Metchnikoff,  Madame,  3. 

Methaemoglobinuria,  234. 

Methods  of  investigation,  111,  115, 
116,  125,  133;  cultures  in 
seven-day  flasks,  135;  gas 
formation,  1 18 ;  gas  formation 
in  sugar  bouillon,  126 ;  growth 


Methods  of  investigation  — 

on  milk,  117;  incubation 
method  of  Welch  and  Nuttall, 
118-124;  microscopical  fields, 
111;  products  of  mixed  flora, 
129;  value  of  Gram  stain,  111- 
114. 

Methyl  guanidin,  221. 

Meyer,  148. 

"  Micro-aerophile, "  26. 

Microscopical     fields,    methods    of 
investigation,  111. 

Milk,     number     of     bacteria,     60; 
question  of  sterilization,  319. 

Moro,  3,  11,  13,  14,  39,  41,  49,  55,  57. 

Moro  and  Murath,  17,  18. 

Mucous    membrane    of    intestine, 
permeability  for  bacteria,  93. 

Mviller,  232. 

Multiple   neuritis   in   excessive   in- 
testinal putrefaction,  311. 

Murath,  13,  14,  17,  18. 

Muscle   fatigue  in  indol  poisoning, 
254 ;  in  phenol  poisoning,  255. 

Myasthenia  gravis,  256. 

Nencki,  70  (footnote),  227. 

Nesbit,  222,  223,  224. 

Neubauer,  147. 

Neurin,  220,  222,  223. 

Nurslings, 

bacteria  in  intestines,  66; 
action  of  mixed  faecal  flora, 
66;  cultural  peculiarities,  40; 
distribution,  48 ;  infection 
through  anus,  55;  inhibitory 
powers,  13,  14,  15,  16,  17; 
numbers,  51 ;  origin  of  bac- 
teria in  intestines,  53;  prod- 
ucts, 53 ;  spore  formation,  58 ; 
staining  properties,  37,  38,  39. 

Nuttall  and  Thierfelder,  2. 

Oebius,  18. 

Opsonic    index,    in   staphylococcal 

infection,  190. 
Opsonins,  309. 

Origin  of  bacteria  in  intestines,  53. 
Oxalic  acid,  216. 
Oxaluria,  216. 
Oxygen,  distribution  in  intestines, 

29. 


INDEX 


359 


Paracolon  organisms,  14,  158. 

Paratyphoid  bacillus,  10,  168. 

Park,  110,  173. 

Passini,  18,  46,  200. 

Pasteur,  2,  23,  27. 

Pathogenicity  of  anaerobes,  117. 

Pentamethylendiamin,  224. 

Peptic  ferment,  6. 

Pernicious  anaemia,  B.  aerogenes 
capsulatus,  312. 

Petruschky,  158  (footnote). 

Pfeiffer,  162. 

Phenol,  20,  237,  247;  in  bacterial 
cultures,  135,  136;  in  bottle- 
fed  children,  68 ;  in  marasmus, 
286;  influence  on  muscles, 
255. 

Phenol-potassium-sulphate,   238. 

Phylogenetic  significance  of  large 
intestine,  97. 

Pizenti,  260. 

Plague  bacillus,  162. 

Porcher  and  Hervieux,  272,  273. 

Progressive  muscular  atrophy,  with 
indicanuria,  276. 

Propionic  acid,  218,  293. 

Proteolytic  action,  6. 

Ptomaines,  226. 

Putrefaction,  intestinal,  aromatic 
products,  237;  indolic  type, 
279,  280 ;  influence  of  prompt 
resorption,  99;  mixed  type, 
279,  306 ;  nervous  manifesta- 
tions, 309 ;  in  production  of 
fatigue,  286;  production  of 
parenchymatous  degeneration, 
309;  prognosis,  337-339;  sac- 
charo-butyric  type,  279,  291; 
treatment,  314;  types,  278. 

Putrefactive  processes,  214. 

Putrescin,  220,  224,  226. 

Reaction,  influence  on  growth  and 
products  of  intestinal  anee- 
robes,  21. 

Receptors,  275. 

Reducing  action  of  meat,  90. 

Resorption  from  small  intestine, 
99. 

Rettger,  24. 

Richards  and  Rowland,  248,  270. 

Rodella,  63,  195. 


Roget,  95. 
Roos,  225. 

Saccharo-butyric  type  of  intestinal 
putrefaction,  279,  291 ;  anae- 
mia, 303 ;  carbon  dioxide  for- 
mation, 294 ;  characteristics 
of  faeces,  293,  294;  conse- 
quences, 299;  ethereal  sul- 
phates, 296;  gas  formation, 
292;  hydrogen  formation,  294. 

Saprophytic  bacteria,  7,  162. 

Sarcinse  in  bottle-fed  children,  63. 

Schardinger,  220. 

Schottelius,  3. 

Schottenfroh,  45  and  footnote,  125. 

Schmidt,  283. 

Schmidt  and  Strassberger,  52. 

Schmidt's  reaction  for  hydro- 
bilirubin,  144. 

Schotmuller,  168. 

Schottenfroh  and  Grassberger,  63 
(footnote). 

Selmi,  226. 

Senator,  230. 

Senescence,  bacteria  in  intestines, 
75,  77,  78. 

Shiga,  172,  174,  175,  176,  177,  180. 

Simon,  149  (footnote). 

Skatol,  239,  243;  colorimetric 
estimation,  142 ;  determina- 
tion, 139;  Ehrlich  aldehyde 
reaction,  148,  240;  separation 
from  indol,  139. 

Skatol  formation,  in  bacterial 
cultures,  135,  136;  in  bottle- 
fed  babies,  64. 

Skatol-amido-acetic  acid,  243. 

Skatolic  type  of  intestinal  putre- 
faction, 279. 

Smith,  Theobald,  90,  111,  117, 
201,  202. 

Sociological  considerations,  347. 

Soor,  15. 

Spirillum  of  cholera,  28. 

Spore-bearing  bacilli,  in  bottle-fed 
children,  64;  in  cats,  80;  in 
meconium,  58. 

Staphylococcal  infections,  189. 

Staphylococci,  in  bottle-fed  chil- 
dren, 62;  pyogenic,  6;  treat- 
ment by  vaccination,  190. 


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UNIVERSITY  OF  CALIFORNIA  LIBRARY 


